Bone

Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support and protect the various organs of the body, produce red andwhite blood cells and store minerals. Bone tissue is a type of dense connective tissue. Bones come in a variety of shapes and have a complex internal and external structure, are lightweight yet strong and hard, and serve multiple functions. One of the types of tissue that makes up bone is the mineralized osseous tissue, also called bone tissue, that gives it rigidity and a coral-like three-dimensional internal structure. Other types of tissue found in bones include marrow, endosteum, periosteum, nerves, blood vessels and cartilage. At birth, there are over 270 bones in an infant human's body,[1]but many of these fuse together as the child grows, leaving a total of 206 separate bones in a typical adult, not counting numerous small sesamoid bones and ossicles. The largest bone in the human body is the femur and the smallest bones among the 206 are the auditory ossicles.[2]

Functions[edit]
Bones have eleven main functions:

Mechanical[edit]

Protection bones can serve to protect internal organs, such as the skull protecting the brain or the ribs protecting the heart and lungs.

Structure bones provide a frame to keep the body supported. Movement bones provide leverage system for, skeletal muscles, tendons, ligaments and joints function together to generate and transfer forces so that individual body parts or the whole body can be manipulated in three-dimensional space. The interaction between bone and muscle is studied in biomechanics.

Sound transduction bones are important in the mechanical aspect of overshadowed hearing.

Synthetic[edit]

Blood production the marrow, located within the medullary cavity of long bones and interstices of cancellous bone, produces blood cells in a process called hematopoiesis.[3]

Metabolic[edit]

Mineral storage bones act as reserves of minerals important for the body, most notably calcium and phosphorus.[citation
needed]

Growth factor storage mineralized bone matrix stores important growth factors such as insulin-like growth factors, transforming growth factor, bone morphogenetic proteins and others.[citation needed]

Fat storage the yellow bone marrow acts as a storage reserve of fatty acids.[citation needed] Acid-base balance bone buffers the blood against excessive pH changes by absorbing or releasing alkaline salts.[citation
needed]

Detoxification bone tissues can also store heavy metals and other foreign elements, removing them from the blood and reducing their effects on other tissues. These can later be gradually released for excretion.[citation needed]

Endocrine organ bone controls phosphate metabolism by releasing fibroblast growth factor 23 (FGF-23), which acts on kidneys to reduce phosphate reabsorption. Bone cells also release a hormone called osteocalcin, which contributes to the regulation of blood sugar (glucose) and fat deposition. Osteocalcin increases both the insulin secretion and sensitivity, in addition to boosting the number of insulin-producing cells and reducing stores of fat.[4]

Mechanical properties[edit]

The primary tissue of bone, osseous tissue, is a relatively hard and lightweight composite material. It is mostly made up of a composite material incorporating the mineral calcium phosphate in the chemical arrangement termed calcium hydroxylapatite (this is the osseous tissue that gives bones their rigidity) and collagen, an elastic protein which improves fracture resistance. It has relatively high compressive strength of about 170 MPa (1800 kgf/cm)[5] but poor tensile strength of 104121 MPa and very low shear stress strength (51.6 MPa),[6] meaning it resists pushing forces well, but not pulling or torsional forces. While bone is essentially brittle, it does have a significant degree of elasticity, contributed chiefly by collagen. All bones consist of living cells embedded in the mineralized organic matrix that makes up the osseous tissue.

Structure[edit]
Bone structure[edit]

An illustration

Bone is not a uniformly solid material, but rather has some spaces between its hard elements. [citation needed]

Compact (cortical) bone[edit]

The hard outer layer of bones is composed of compact bone tissue, so-called due to its minimal gaps and spaces. Its porosity is 530%.[7] This tissue gives bones their smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adultskeleton. Compact bone may also be referred to as dense bone.[citation needed]

Trabecular (cancellous or spongy) bone[edit]

Filling the interior of the bone is the trabecular bone tissue (an open cell porous network also called cancellous or spongy bone), which is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass but has nearly ten times the surface area of compact bone. Its porosity is 3090%.[7] If, for any reason, there is an alteration in the strain the cancellous is subjected to, there is a rearrangement of the trabeculae. The microscopic difference between compact and cancellous bone is that compact bone consists of haversian sites and osteons, while cancellous bones do not. Also, bone surrounds blood in the compact bone, while blood surrounds bone in the cancellous bone.[citation needed]

Cellular structure[edit]
There are several types of cells constituting the typical bone:

Osteoblasts are mononucleate bone-forming cells that descend from osteoprogenitor cells. They are located on the surface of osteoid seams and make a protein mixture known as osteoid, which mineralizes to become bone. The osteoid seam is a narrow region of newly formed organic matrix, not yet mineralized, located on the surface of a bone. Osteoid is primarily composed of Type I collagen. Osteoblasts also manufacture hormones, such as prostaglandins, to act on the bone itself. They robustly produce alkaline phosphatase, an enzyme that has a role in the mineralisation of bone, as well as

many matrix proteins. Osteoblasts are the immature bone cells, and eventually become entrapped in the bone matrix to become osteocytes- the mature bone cell.[citation needed]

Bone lining cells are essentially inactive osteoblasts. They cover all of the available bone surface and function as a barrier for certainions.[citation needed]

Osteocytes originate from osteoblasts that have migrated into and become trapped and surrounded by bone matrix that they themselves produce. The spaces they occupy are known as lacunae. Osteocytes have many processes that reach out to meet osteoblasts and other osteocytes probably for the purposes of communication. Their functions include, to varying degrees: formation of bone; matrix maintenance; and calcium homeostasis. They have also been shown to act as mechano-sensory receptors regulating the bone's response to stress and mechanical load. They are mature bone cells.[citation needed]

Osteoclasts are the cells responsible for bone resorption, thus they break down bone. New bone is then formed by the osteoblasts (remodeling of bone to reduce its volume). Osteoclasts are large, multinucleated cells located on bone surfaces in what are called Howship's lacunae or resorption pits. These lacunae, or resorption pits, are left behind after the breakdown of the bone surface. Because the osteoclasts are derived from a monocyte stem-cell lineage, they are equipped with phagocytic-like mechanisms similar to circulating macrophages. Osteoclasts mature and/or migrate to discrete bone surfaces. Upon arrival, active enzymes, such as tartrate resistant acid phosphatase, are secreted against the mineral substrate.[citation needed]

Molecular structure[edit]
Matrix[edit]
The majority of bone is made of the bone matrix. It is composed primarily of inorganic hydroxyapatite and organic collagen. Bone is formed by the hardening of this matrix around entrapped cells. When these cells become entrapped from osteoblasts they become osteocytes.[citation needed]

Inorganic[edit]
The inorganic composition of bone (bone mineral) is formed from carbonated hydroxyapatite[9][10] (Ca10(PO4)6(OH)2) with lower crystallinity.[9][11] The matrix is initially laid down as unmineralised osteoid (manufactured by osteoblasts). Mineralisation involves osteoblasts secreting vesicles containingalkaline phosphatase. This cleaves the phosphate groups and acts as the foci for calcium and phosphate deposition. The vesicles then rupture and act as a centre for crystals to grow on. More particularly, bone mineral is formed from globular and plate structures,[11][12] distributed among the collagen fibrils of bone and forming yet larger structure.[citation needed]

Organic[edit]
The organic part of matrix is mainly composed of Type I collagen. This is synthesised intracellularly as tropocollagen and then exported, forming fibrils. The organic part is also composed of various growth factors, the functions of which are not fully known. Factors present include glycosaminoglycans,osteocalcin, osteonectin, bone sialo protein, osteopontin and Cell Attachment Factor.[citation needed]

Woven vs. lamellar bone[edit]

Two types of bone can be identified microscopically according to the pattern of collagen forming the osteoid (collagenous support tissue of type I collagen embedded in glycosaminoglycan gel):

Woven bone, which is characterized by haphazard organization of collagen fibers and is mechanically weak [citation needed]

Lamellar bone, which has a regular parallel alignment of collagen into sheets (lamellae) and is mechanically strong [citation
needed]

Woven bone is produced when osteoblasts produce osteoid rapidly, which occurs initially in all fetal bones (but is later replaced by more resilient lamellar bone). In adults woven bone is created after fractures or in Paget's disease. Woven bone is weaker, with a smaller number of randomly oriented collagen fibers, but forms quickly; it is for this appearance of the fibrous matrix that the bone is termed woven. It is soon replaced by lamellar bone, which is highly organized in concentric sheets with a much lower proportion of osteocytes to surrounding tissue. Lamellar bone, which makes its first appearance in the fetus during the third trimester,[13] is stronger and filled with many collagen fibers parallel to other fibers in the same layer (these parallel columns are called osteons). In cross-section, the fibers run in opposite directions in alternating layers, much like in plywood, assisting in the bone's ability to resist torsion forces. After a fracture, woven bone forms initially and is gradually replaced by lamellar bone during a process known as "bony substitution." Compared to woven bone, lamellar bone formation takes place more slowly. The orderly deposition of collagen fibers restricts the formation of osteoid to about 1 to 2 m per day. Lamellar bone also requires a relatively flat surface to lay the collagen fibers in parallel or concentric layers. [citation needed] These terms are histologic, in that a microscope is necessary to differentiate between the two.[citation needed]

Types[edit]

There are five types of bones in the human body: long, short, flat, irregular, and sesamoid.

Long bones are characterized by a shaft, the diaphysis, that is much longer than it is wide. They are made up mostly of compact bone, with lesser amounts of marrow, located within the medullary cavity, and spongy bone. Most bones of the limbs, including those of the fingers andtoes, are long bones. The exceptions are those of the wrist, ankle and kneecap.[citation needed]

Short bones are roughly cube-shaped, and have only a thin layer of compact bone surrounding a spongy interior. The bones of the wrist and ankle are short bones, as are the sesamoid bones.[citation needed]

Flat bones are thin and generally curved, with two parallel layers of compact bones sandwiching a layer of spongy bone. Most of the bones of the skull are flat bones, as is the sternum.[citation needed]

Sesamoid bones are bones embedded in tendons. Since they act to hold the tendon further away from the joint, the angle of the tendon is increased and thus the leverage of the muscle is increased. Examples of sesamoid bones are the patella and the pisiform.[citation needed]

Irregular bones do not fit into the above categories. They consist of thin layers of compact bone surrounding a spongy interior. As implied by the name, their shapes are irregular and complicated. Often this irregular shape is due to their many centers of ossification or because they contain bony sinuses. The bones of the spine, Pelvis, and some bones of the skull are irregular bones. Examples include the ethmoid and sphenoidbones.[14]

Formation[edit]
The formation of bone during the fetal stage of development occurs by two processes: Intramembranous ossification and endochondral ossification.[citation needed]

Intramembranous ossification[edit]
Intramembranous ossification mainly occurs during formation of the flat bones of the skull but also the mandible, maxilla, and clavicles; the bone is formed from connective tissue such asmesenchyme tissue rather than from cartilage. The steps in intramembranous ossification are:[citation needed] 1. Development of ossification center 2. Calcification 3. Formation of trabeculae 4. Development of periosteum

Endochondral ossification[edit]

Endochondral ossification, on the other hand, occurs in long bones and most of the rest of the bones in the body; it involves an initial hyaline cartilage that continues to grow. The steps in endochondral ossification are: [citation needed] 1. Development of cartilage model 2. Growth of cartilage model 3. Development of the primary ossification center 4. Development of the secondary ossification center 5. Formation of articular cartilage and epiphyseal plate

Endochondral ossification begins with points in the cartilage called "primary ossification centers." They mostly appear during fetal development, though a few short bones begin their primary ossification after birth. They are responsible for the formation of the diaphyses of long bones, short bones and certain parts of irregular bones. Secondary ossification occurs after birth, and forms the epiphyses of long bones and the extremities of irregular and flat bones. The diaphysis and both epiphyses of a long bone are separated by a growing zone of cartilage (the epiphyseal plate). When the child reaches skeletal maturity (18 to 25 years of age), all of the cartilage is replaced by bone, fusing the diaphysis and both epiphyses together (epiphyseal closure).[citation needed] In the upper limbs, only the diaphyses of the long bones and scapula are ossified. The epiphyses, carpal bones, coracoid process, medial border of the scapula, and acromion are still cartilaginous.[15] The following steps are followed in the conversion of cartilage to bone: 1. Zone of reserve cartilage. This region, farthest from the marrow cavity, consists of typical hyaline cartilage that as yet shows no sign of transforming into bone.[16] 2. Zone of cell proliferation. A little closer to the marrow cavity, chondrocytes multiply and arrange themselves into longitudinal columns of flattened lacunae.[16] 3. Zone of cell hypertrophy. Next, the chondrocytes cease to divide and begin to hypertrophy (enlarge), much like they do in the primary ossification center of the fetus. The walls of the matrix between lacunae become very thin.[16] 4. Zone of calcification. Minerals are deposited in the matrix between the columns of lacunae and calcify the cartilage. These are not the permanent mineral deposits of bone, but only a temporary support for the cartilage that would otherwise soon be weakened by the breakdown of the enlarged lacunae.[16] 5. Zone of bone deposition. Within each column, the walls between the lacunae break down and the chondrocytes die. This converts each column into a longitudinal channel, which is immediately invaded by blood vessels and marrow from the marrow cavity. Osteoblasts line up along the walls of these channels and begin depositing concentric lamellae of matrix, while osteoclasts dissolve the temporarily calcified cartilage.[16]

Bone marrow[edit]
Bone marrow can be found in almost any bone that holds cancellous tissue. In newborns, all such bones are filled exclusively with red marrow, but as the child ages it is mostly replaced by yellow, or fatty marrow. In adults, red marrow is mostly found in the marrow bones of the femur, the ribs, the vertebrae and pelvic bones.[citation needed]

Remodeling[edit]
Remodeling or bone turnover is the process of resorption followed by replacement of bone with little change in shape and occurs throughout a person's life. Osteoblasts and osteoclasts, coupled together via paracrine cell signalling, are referred to as bone remodeling unit. Approximately 10% of the skeletal mass of an adult is remodelled each year. [17]

Purpose[edit]
The purpose of remodeling is to regulate calcium homeostasis, repair micro-damaged bones (from everyday stress) but also to shape and sculpt the skeleton during growth.[citation needed]

Calcium balance[edit]
The process of bone resorption by the osteoclasts releases stored calcium into the systemic circulation and is an important process in regulating calcium balance. As bone formation actively fixescirculating calcium in its mineral form, removing it from

the bloodstream, resorption actively unfixes it thereby increasing circulating calcium levels. These processes occur in tandem at site-specific locations.[citation needed]

Bone volume[edit]
Bone volume is determined by the rates of bone formation and bone resorption. Recent research has suggested that certain growth factors may work to locally alter bone formation by increasing osteoblast activity. Numerous bone-derived growth factors have been isolated and classified via bone cultures. These factors include insulin-like growth factors I and II, transforming growth factor-beta, fibroblast growth factor, platelet-derived growth factor, and bone morphogenetic proteins.[18] Evidence suggests that bone cells produce growth factors for extracellular storage in the bone matrix. The release of these growth factors from the bone matrix could cause the proliferation of osteoblast precursors. Essentially, bone growth factors may act as potential determinants of local bone formation.[18] Research has suggested that trabecular bone volume in postemenopausal osteoporosis may be determined by the relationship between the total bone forming surface and the percent of surface resorption.[19]

Repair[edit]
Repeated stress, such as weight-bearing exercise or bone healing, results in the bone thickening at the points of maximum stress (Wolff's law). It has been hypothesized that this is a result of bone's piezoelectric properties, which cause bone to generate small electrical potentials under stress.[20]

Paracrine cell signalling[edit]

The action of osteoblasts and osteoclasts are controlled by a number of chemical factors that either promote or inhibit the activity of the bone remodeling cells, controlling the rate at which bone is made, destroyed, or changed in shape. The cells also use paracrine signalling to control the activity of each other.[citation needed]

Osteoblast stimulation[edit]
Osteoblasts can be stimulated to increase bone mass through increased secretion of osteoid and by inhibiting the ability of osteoclasts to break down osseous tissue.[citation needed] Bone building through increased secretion of osteoid is stimulated by the secretion of growth hormone by the pituitary, thyroid hormone and the sex hormones (estrogens and androgens). These hormones also promote increased secretion of osteoprotegerin.[21] Osteoblasts can also be induced to secrete a number of cytokines that promote reabsorbtion of bone by stimulating osteoclast activity and differentiation from progenitor cells. Vitamin D, parathyroid hormone and stimulation from osteocytes induce osteoblasts to increase secretion of RANK-ligand and interleukin 6, which cytokines then stimulate increased reabsorption of bone by osteoclasts. These same compounds also increase secretion of macrophage colony-stimulating factor by osteoblasts, which promotes the differentiation of progenitor cells into osteoclasts, and decrease secretion of osteoprotegerin.[citation needed]

Osteoclast inhibition[edit]
The rate at which osteoclasts resorb bone is inhibited by calcitonin and osteoprotegerin. Calcitonin is produced by parafollicular cells in the thyroid gland, and can bind to receptors on osteoclasts to directly inhibit osteoclast activity. Osteoprotegerin is secreted by osteoblasts and is able to bind RANK-L, inhibiting osteoclast stimulation.[21]

HORMONES INVOLVED IN BONE METABOLISM AND REMODELLING The main hormones involved in bone metabolism and remodelling are parathyroid hormone (PTH), members of the vitamin D family, oestrogens and calcitonin. Glucocorticoids and thyroid hormone also affect bone.

PARATHYROID HORMONE Parathyroid hormone, which consists of a single-chain polypeptide of 84 amino acids, is an important physiological regulator of Ca2+ metabolism. It acts on PTH receptors in various tissues (bone, kidney, gastrointestinal tract) to maintain the plasma Ca2+ concentration. It mobilises Ca2+ from bone, promotes its reabsorption by the kidney and stimulates the synthesis of calcitriol, which in turn increases Ca2+absorption from the intestine and synergises with PTH in mobilising bone Ca2+ (Figs 35.3 and 35.4). PTH promotes phosphate excretion, and thus its net effect is to increase the concentration of Ca2+ in the plasma and lower that of phosphate. The mobilisation of Ca2+ from bone by PTH is mediated, at least in part, by stimulation of the recruitment and activation of osteoclasts. Pathological oversecretion of PTH (hyperparathyroidism) inhibits osteoblast activity (not shown in Fig. 35.1). But given therapeutically in a low intermittent dose, PTH and fragments of PTH paradoxically stimulate osteoblast activity and enhance bone formation. Parathyroid hormone is synthesised in the cells of the parathyroid glands and stored in vesicles. The principal factor controlling secretion is the concentration of ionised calcium in the plasma, low plasma Ca2+ stimulating secretion, high plasma Ca2+ decreasing it by binding to and activating a Ca2+-sensing Gprotein-coupled surface receptor (see Ch. 3, Figure 35.3). (For reviews, see Stewart, 2004; Deal, 2009.) VITAMIN D Vitamin D (calciferol) consists of a group of lipophilic prehormones that are converted in the body into a number of biologically active metabolites that function as true hormones, circulating in the blood and regulating the activities of various cell types (see Reichel et al., 1989). Their main action, mediated by nuclear receptors of the steroid receptor superfamily (see Ch. 3), is the maintenance of plasma Ca2+ by increasing Ca2+ absorption in the intestine, mobilising Ca2+ from bone and decreasing its renal excretion (see Fig. 35.3). In humans, there are two sources of vitamin D: 1. Dietary ergocalciferol (D2), derived from ergosterol in plants. 2. Cholecalciferol (D3) generated in the skin from 7-dehydrocholesterol by the action of ultraviolet irradiation, the 7dehydrocholesterol having been formed from cholesterol in the wall of the intestine. Cholecalciferol is converted to calcifediol (25-hydroxy-vitamin D3) in the liver, and this is converted to a series of other metabolites of varying activity in the kidney, the most potent of which is calcitriol (1,25-dihydroxyvitamin D3); see Fig. 35.4). The synthesis of calcitriol from calcifediol is regulated by PTH, and is also influenced by the phosphate concentration in the plasma and by the calcitriol concentration itself through a negative feedback mechanism (Fig. 35.4). Receptors for calcitriol are ubiquitous, and calcitriol is important in the functioning of many cell types. The main actions of calcitriol are the stimulation of absorption of Ca2+ and phosphate in the intestine, and the mobilisation of Ca2+ from bone, but it also increases Ca2+ reabsorption in the kidney tubules (Fig. 35.3). Its effect on bone involves promotion of maturation of osteoclasts and indirect stimulation of their activity ( Figs 35.1 and 35.3). It decreases collagen synthesis by osteoblasts. However, the effect on bone is complex and not confined to mobilising Ca2+, because in clinical vitamin D deficiency (see below), in which the mineralisation of

bone is impaired, administration of vitamin D restores bone formation. One explanation may lie in the fact that calcitriol stimulates synthesis of osteocalcin, the Ca2+-binding protein of bone matrix. OESTROGENS During reproductive life in the female, oestrogens have an important role in maintenance of bone integrity, acting on both osteoblasts and osteoclasts. They inhibit the cytokines that recruit osteoclasts and oppose the bone-resorbing, Ca2+-mobilising action of PTH. They increase osteoblast proliferation, augment the production of TGF- and bone morphogenic proteins, and inhibit apoptosis (see Ch. 5). Withdrawal of oestrogen, as happens at the menopause, can (and usually does) lead to osteoporosis. Parathyroid, vitamin D and bone mineral homeostasis

The vitamin D family are true hormones; precursors are converted to calcifediol in the liver, then to the main hormone, calcitriol, in the kidney. Calcitriol increases plasma Ca2+ by mobilising it from bone, increasing its absorption in the intestine and decreasing its excretion by the kidney. Parathyroid hormone (PTH) increases blood Ca2+ by increasing calcitriol synthesis, mobilising Ca2+from bone and reducing renal Ca2+ excretion. (But, paradoxically, small doses of PTH given intermittently increase bone formation.) Calcitonin (secreted from the thyroid) reduces Ca2+ resorption from bone by inhibiting osteoclast activity. CALCITONIN Calcitonin is a peptide hormone secreted by the specialised C cells found in the thyroid follicles (see Ch. 33). The main action of calcitonin is on bone; it inhibits bone resorption by binding to a specific receptor on osteoclasts, inhibiting their action. In the kidney, it decreases the reabsorption of both Ca2+ and phosphate in the proximal tubules. Its overall effect is to decrease the plasma Ca2+ concentration (Fig. 35.3). Secretion is determined mainly by the plasma Ca2+ concentration. OTHER HORMONES Physiological concentrations of glucocorticoids are required for osteoblast differentiation. Excessive pharmacological concentrations inhibit bone formation by inhibiting osteoblast differentiation and activity, and may stimulate osteoclast actionleading to osteoporosis, which is a feature of Cushings syndrome (Fig. 32.7) and an important adverse effect of glucocorticoid administration (Ch. 32). Thyroxine stimulates osteoclast action, reducing bone density and liberating Ca2+. Osteoporosis occurs in association with thyrotoxicosis, and care must be taken not to use excessive thyroxine dosage for treating hypothyroidism (see Ch. 33).

Lumbar vertebrae
In human anatomy, the lumbar vertebrae are the five vertebrae between the rib cage and the pelvis. They are the largest segments of the vertebral column and are characterized by the absence of the foramen transversarium within the transverse process (as it is only found in the cervical region), and by the absence of facets on the sides of the body. They are designated L1 to L5, starting at the top. The lumbar vertebrae help support the weight of the body, and permit movement.

Human anatomy[edit]
General characteristics[edit]

Lumbar vertebrae

These are the general characteristics of the first through fourth lumbar vertebrae. The fifth vertebra contains certain peculiarities, which are detailed below. As with other vertebrae, each lumbar vertebra consists of a vertebral body and a vertebral arch. The vertebral arch, consisting of a pair of pedicles and a pair of laminae, encloses the vertebral foramen(opening) and supports seven processes.

Body[edit]
The vertebral body of each lumbar vertebra is large, wider from side to side than from front to back, and a little thicker in front than in back. It is flattened or slightly concave above and below, concave behind, and deeply constricted in front and at the sides.[1]

Arch[edit]
The pedicles are very strong, directed backward from the upper part of the vertebral body; consequently, the inferior vertebral notches are of considerable depth.[1] The pedicles change in morphology from the upper lumbar to the lower lumbar. They increase in sagittal width from 9 mm to up to 18 mm at L5. They increase in angulation in the axial plane from 10 degrees to 20 degrees by L5. The pedicle is sometimes used as a portal of entrance into the vertebral body for fixation with pedicle screws or for placement of bone cement as with kyphoplasty or vertebroplasty. The laminae are broad, short, and strong.[1] They form the posterior portion of the vertebral arch. In the upper lumbar region the lamina are taller than wide but in the lower lumbar vertebra the lamina are wider than tall. The lamina connect the spinous process to the pedicles. The vertebral foramen within the arch is triangular, larger than in the thoracic vertebrae, but smaller than in the cervical vertebrae.[1]

Processes[edit]
The spinous process is thick, broad, and somewhat quadrilateral; it projects backward and ends in a rough, uneven border, thickest below where it is occasionally notched.[1] The superior and inferior articular processes are well-defined, projecting respectively upward and downward from the junctions of pedicles and laminae. The facets on the superior processes are concave, and look backward and medialward; those on the inferior are convex, and are directed forward and lateralward. The former are wider apart than the latter, since in the articulated column the inferior articular processes are embraced by the superior processes of the subjacent vertebra. [1] The transverse processes are long and slender. They are horizontal in the upper three lumbar vertebrae and incline a little upward in the lower two. In the upper three vertebrae they arise from the junctions of the pedicles and laminae, but in the lower two they are set farther forward and spring from the pedicles and posterior parts of the vertebral bodies. They are situated in front of the articular processes instead of behind them as in the thoracic vertebrae, and are homologous with the ribs.[1]

Three portions or tubercles can be noticed in a transverse process of a lower lumbar vertebrae: the lateral or costiform process, the mammillary process, and the accessory process.[2] The costiform is lateral, the mammillary is superior (cranial), and the accessory is inferior (caudal). The mammillary is connected in the lumbar region with the back part of the superior articular process.[clarification needed] The accessory process is situated at the back part of the base of the transverse process. The tallest and thickest costiform process is usually that of L5.[2]

First and fifth lumbar vertebrae[edit]

The first lumbar vertebra is level with the anterior end of the ninth rib. This level is also called the important transpyloric plane, since the pylorus of the stomach is at this level. The fifth lumbar vertebra is characterized by its body being much deeper in front than behind, which accords with the prominence of the sacrovertebral articulation; by the smaller size of its spinous process; by the wide interval between the inferior articular processes, and by the thickness of its transverse processes, which spring from the body as well as from the pedicles.[1] The fifth lumbar vertebra is by far the most common site ofspondylolysis and spondylolisthesis.[3] Most individuals have five lumbar vertebrae, while some have four or six. Lumbar disorders that normally affect L5 will affect L4 or L6 in these latter individuals.

Segmental movements[edit]
The range of segmental movements in a single segment is difficult to measure clinically, not only because of variations between individuals, but also because it is age and gender dependent. Furthermore, flexion and extension in the lumbal spine is the product of a combination of rotation and translation in the sagittal plane between each vertebra. [4] Ranges of segmental movements in the lumbal spine (White and Panjabi, 1990) are (in degrees): [5]

L1-L2 L2-L3 L3-L4 L4-L5 L5-S1

Flexion/ 12 Extension

14

15

16

17

Lateral flexion

Axial rotation

Variation[edit]
Lumbarization is a term that refers to an anatomic anomaly in the human spine. It is defined by the nonfusion of the first and second segments of thesacrum. The lumbar spine subsequently appears to have six vertebrae or segments, not five. Conversely the sacrum appears to have only four segments instead of its designated five segments. [6] Sacralization of the fifth lumbar vertebra (or sacralization) is a congenital anomaly, in which the transverse process of the last lumbar vertebra (L5) fuses to the sacrum on one side or both, or to ilium, or both. These anomalies are observed at about 3.5 percent of people, and it is usually bilateral. Although sacralization may be a cause of low back pain, it is asymptomatic in many cases (especially bilateral type). Low back pain in these cases most likely occurs due to chronic faulty biomechanics. In sacralization, the L5-S1 intervertebral disc may be thin and narrow. This abnormality is found by X-ray

Intervertebral joints: Joining other vertebrae to each other

Definition: The intervertebral joint is the space that is located between any two adjacent vertebrae. This space allows movement to occur in the spine. The meeting points of the two spinal bones involved in forming an intervertebral joint are the vertebral body (the front portion) and the vertebral arch (the back portion). Between the vertebral bodies, cushioning is provided by the presence of intervertebral discs.

The spine has ligaments made of tough fibrous bands of connective tissue that help stabilize the intervertebral joints and support the spinal column in weight bearing and movement.
Examples: Movement in all directions (forward, back, side to side and twisting) occurs at the many intervertebral joints in spine. Intervertebral joints, which connect adjacent vertebrae, include both synovial and cartilaginous joints.

Intervertebral synovial joints: These joints are found between the superior and inferior facets of adjoining vertebral arches. They are supported by the following ligaments:

The interspinous ligament runs between the spinous processes. The supraspinous ligament connects the tips of the spinous processes and forms the strong nuchal ligament that runs posterior to the cervical spine.

Intertransverse ligaments connect the adjacent transverse processes, and the ligamentum flavum connects the laminae of adjoining vertebrae.

Intervertebral cartilaginous joints: A fibrocartilaginous joint is formed between the adjacent vertebral bodies with fibrocartilaginous intervertebral discs located between the bodies. Each disc is made up of a gelatinous mass, the nucleus pulposus, which is surrounded by the annulus fibrosus (which is made up of tough fibrous layers). Anterior and posterior longitudinal ligaments run in bands down the anterior and posterior surfaces of the vertebral bodies from the skull to the sacrum. They help to stabilize the vertebral column.

Causes A healthy intervertebral disc has a great deal of water in the nucleus pulposus (the center portion of the disc). The water content gives the nucleus a spongy quality and allows it to absorb spinal stress. Excessive pressure or injuries to the disc can cause the injury to the annulus (the outer ring of tough ligament material) that holds the vertebrae together. The annulus is generally the first portion of the disc to be injured. Small tears show up in the ligament material of the annulus. These tears heal by scar tissue, which is not as strong as normal ligament tissue. The annulus becomes weaker over time as more scar tissue forms. This can lead to damage of the nucleus pulposus. It begins to lose its water content and dry up. View animation of degeneration. Loss of water content causes the discs to lose some of their ability to act as cushions. This can lead to even more stress on the annulus and still more tears as the cycle repeats itself. As the nucleus loses its water content, it collapses. Without the cushion effect of the discs, the vertebrae in your spine would not be able to absorb stresses or provide the movement needed to bend and twist. collapses, allowing the two vertebrae above and below to move closer to one another. This results in a narrowing of the disc space between the two vertebrae. As this shift occurs, the facet joints (located at the back of the spine) are forced to shift. Shifting changes the way the facet joints work together and can cause problems as well. Bone spurs, sometimes called osteophytes, may begin to form around the disc space. These can also form around the facet joints. This is thought to be due to the body's response to try to stop the excess motion at the spinal segment. The bone spurs can become a problem if they start to grow into the spinal canal and press into the spinal cord and spinal nerves. This condition is called spinal stenosis.

Practice Essentials

Osteoporosis is the most common metabolic bone disease in the United States and can result in devastating physical, psychosocial, and economic consequences. It is often overlooked and undertreated, however, in large part because it is so often clinically silent before manifesting in the form of fracture.

Essential update: New osteoporosis diagnosis and management guidelines

In June 2013, the National Osteoporosis Guideline Group (NOGG) updated its guidelines on the diagnosis and management of osteoporosis in postmenopausal women and men at least 50 years of age in the United Kingdom. Recommendations include the following[1, 2] : Pharmacotherapies shown to lower the risk for vertebral fracture (and for hip fracture in some cases) include bisphosphonates, denosumab, parathyroid hormone peptides, raloxifene, and strontium ranelate Generic alendronate is usually first-line treatment because of its broad spectrum of anti-fracture efficacy and low cost Ibandronate, risedronate, zoledronic acid, denosumab, raloxifene, or strontium ranelate may be appropriate therapy if alendronate is contraindicated or poorly tolerated Because of their high cost, parathyroid hormone peptides should be used only for patients at very high risk, especially for vertebral fractures Postmenopausal women may benefit from calcitriol, etidronate, and hormone replacement therapy Treatments for men at increased fracture risk include alendronate, risedronate, zoledronic acid, and teriparatide Patients at increased risk for fracture should start alendronate or other bone-protective treatment at the onset of glucocorticoid therapy For postmenopausal women, pharmacotherapy for prevention and treatment of glucocorticoid-induced osteoporosis includes alendronate, etidronate, and risedronate; treatment options for both sexes are teriparatide and zoledronic acid Calcium and vitamin D supplementation is widely recommended for older persons who are housebound or live in residential or nursing homes and is often recommended as an adjunct to other treatments for osteoporosis Potential adverse cardiovascular effects of calcium supplementation are controversial, but it may be prudent to increase dietary calcium intake and use vitamin D alone rather than using both calcium and vitamin D supplementation Withdrawal of bisphosphonate treatment is associated with decreases in BMD and bone turnover after 2-3 years for alendronate and 1-2 years for ibandronate and risedronate Continuation of bisphosphonates without the need for further evaluation is recommended for high-risk individuals; when bisphosphonates are continued, treatment review, including renal function evaluation, is needed every 5 years If bisphosphonates are discontinued, fracture risk should be reevaluated after every new fracture, or after 2 years if no new fracture occurs After 3 years of zoledronic acid treatment, the benefits on BMD density persist for at least another 3 years after discontinuation; most patients should stop treatment after 3 years, and their physician should review the need for continuation of therapy 3 years later Persons with a previous vertebral fracture or a pretreatment hip BMD T-score of 2.5 SD or less may be at increased risk for vertebral fracture if zoledronic acid is discontinued

Signs and symptoms

Osteoporosis generally does not become clinically apparent until a fracture occurs. Two thirds of vertebral fractures are painless. Typical findings in patients with painful vertebral fractures may include the following: The episode of acute pain may follow a fall or minor trauma Pain is localized to a specific, identifiable, vertebral level in the midthoracic to lower thoracic or upper lumbar spine The pain is described variably as sharp, nagging, or dull; movement may exacerbate pain; in some cases, pain radiates to the abdomen Pain is often accompanied by paravertebral muscle spasms exacerbated by activity and decreased by lying supine Patients often remain motionless in bed because of fear of causing an exacerbation of pain Acute pain usually resolves after 4-6 weeks; in the setting of multiple fractures with severe kyphosis, the pain may become chronic Patients who have sustained a hip fracture may experience the following: Pain in the groin, posterior buttock, anterior thigh, medial thigh, and/or medial knee during weight-bearing or attempted weight-bearing of the involved extremity Diminished hip range of motion (ROM), particularly internal rotation and flexion External rotation of the involved hip while in the resting position On physical examination, patients with vertebral compression fractures may demonstrate the following: With acute vertebral fractures, point tenderness over the involved vertebra Thoracic kyphosis with an exaggerated cervical lordosis (dowager hump) Subsequent loss of lumbar lordosis A decrease in height of 2-3 cm after each vertebral compression fracture and progressive kyphosis Patients with hip fractures may demonstrate the following: Limited ROM with end-range pain on a FABER (flexion in abduction and external rotation) hip joint test Decreased weight-bearing on the fractured side or an antalgic gait pattern Patients with pubic and sacral fractures may have the following:

Marked pain with ambulation Tenderness to palpation, percussion, or both With sacral fractures, pain with physical examination techniques used to assess the sacroiliac joint (eg, FABER, Gaenslen, or squish test) Balance difficulties may be evident, especially in patients with an altered center of gravity from severe kyphosis. [3] Patients may have difficulty performing tandem gait and performing single limb stance. See Clinical Presentation for more detail.

Diagnosis
Baseline laboratory studies include the following: Complete blood count: May reveal anemia or raise suspicion of alcoholism Serum chemistry levels: Usually normal in persons with primary osteoporosis Serum iron and ferritin levels: Helpful when malabsorption or hemochromatosis is suspected Liver function tests: Elevations may indicate alcoholism Thyroid-stimulating hormone level: Thyroid dysfunction has been associated with osteoporosis 25-Hydroxyvitamin D level: Vitamin D insufficiency can predispose to osteoporosis Bone mineral density (BMD) measurement is recommended in the following patients [4, 5] : Women aged 65 years or older and men aged 70 years or older, regardless of clinical risk factors Younger postmenopausal women and men aged 50-70 years with clinical risk factors for fracture Women in menopausal transition with a specific risk factor associated with increased risk for fracture (ie, low body weight, prior low-trauma fracture, use of a high-risk medication) Adults with fragility fractures Adults who have a condition associated with low bone mass or bone loss (eg, rheumatoid arthritis) Adults who take a medication associated with low bone mass or bone loss (eg, glucocorticoids, 5 mg of prednisone daily for 3 mo) Anyone being considered for pharmacologic therapy for osteoporosis Anyone being treated for osteoporosis (to monitor treatment effect) Anyone not receiving therapy in whom evidence of bone loss would lead to treatment Dual-energy x-ray absorptiometry (DXA) is currently the criterion standard for the evaluation of BMD.[5, 6] Peripheral DXA is used to measure BMD at the wrist; it may be most useful in identifying patients at very low fracture risk who require no further workup. DXA provides the patients T-score, which is the BMD value compared with that of control subjects who are at their peak BMD.[7, 8, 9, 10] World Health Organization (WHO) criteria define a normal T-score value as within 1 standard deviation (SD) of the mean BMD value in a healthy young adult. Values lying farther from the mean are stratified as follows [9] : T-score of 1 to 2.5 SD indicates osteopenia T-score of less than 2.5 SD indicates osteoporosis T-score of less than 2.5 SD with fragility fracture(s) indicates severe osteoporosis DXA also provides the patients Z-score, which reflects a value compared with that of persons matched for age and sex. Z-scores adjusted for ethnicity or race should be used in the following patients: Premenopausal women Men younger than 50 years Children Z-score values of 2.0 SD or lower are defined as "below the expected range for age" and those above 2.0 SD as "within the expected range for age." The diagnosis of osteoporosis in these groups should not be based on densitometric criteria alone. Quantitative calcaneal ultrasonography offers the following benefits [11] : As effective as DXA at predicting femoral neck, hip, and spine fractures Lower cost than DXA More portability than DXA No exposure to ionizing radiation However, no diagnostic criteria based on quantitative ultrasonography or a combination of quantitative ultrasonography and DXA have been defined. Plain radiography features and recommendations are as follows: Obtain radiographs of the affected area in symptomatic patients Lateral spine radiography can be performed in asymptomatic patients in whom a vertebral fracture is suspected; a scoliosis series is useful for detecting occult vertebral fractures Radiographic findings can suggest the presence of osteopenia, or bone loss, but cannot be used to diagnose osteoporosis

Radiographs may also show other conditions, such as osteoarthritis, disk disease, or spondylolisthesis See Workup for more detail.

Management
Lifestyle modification for prevention of osteoporotic fractures includes the following [12] : Increasing weight-bearing and muscle-strengthening exercise Ensuring optimum calcium and vitamin D intake as an adjunct to active antifracture therapy The National Osteoporosis Foundation (NOF) recommends that pharmacologic therapy should be reserved for postmenopausal women and men aged 50 years or older who present with the following[4] : A hip or vertebral fracture (vertebral fractures may be clinical or morphometric [ie, identified on a radiograph alone]) T-score of 2.5 or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes Low bone mass (T-score between 1.0 and 2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture of 3% or greater or a 10-year probability of a major osteoporosis-related fracture of 20% or greater based on the USadapted World Health Organization algorithm Guidelines from the American Association of Clinical Endocrinologists include the following recommendations for choosing drugs to treat osteoporosis[13] : First-line agents: Alendronate, risedronate, zoledronic acid, denosumab Second-line agent: Ibandronate Second- or third-line agent: Raloxifene Last-line agent: Calcitonin Treatment for patients with very high fracture risk or in whom bisphosphonate therapy has failed: teriparatide Medical care also includes the identification and treatment of potentially treatable underlying causes of osteoporosis such as hyperparathyroidism and hyperthyroidism. Surgical care includes vertebroplasty and kyphoplasty, which are minimally invasive spine procedures used for the management of painful osteoporotic vertebral compression fractures.

Background
Osteoporosis, a chronic, progressive disease of multifactorial etiology (see Etiology), is the most common metabolic bone disease in the United States. It has been most frequently recognized in elderly white women, although it does occur in both sexes, all races, and all age groups. Screening at-risk populations is essential (see Workup). Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility.[14] The disease often does not become clinically apparent until a fracture occurs (see the following image).. Osteoporosis represents an increasingly serious health and economic problem in the United States and around the world.[15] Many individuals, male and female, experience pain, disability, and diminished quality of life as a result of having this condition. Despite the adverse effects of osteoporosis, it is a condition that is often overlooked and undertreated, in large part because it is so often clinically silent before manifesting in the form of fracture. For example, a Gallup survey performed by the National Osteoporosis Foundation revealed that 86% of all women aged 45-75 years had never discussed osteoporosis with their physicians, and more than 80% were unaware that osteoporosis is directly responsible for disabling hip fractures.[16] Failure to identify at-risk patients, to educate them, and to implement preventive measures may lead to tragic consequences. Medical care includes calcium, vitamin D, and antiresorptive agents such as bisphosphonates, the selective estrogen receptor modulator (SERM) raloxifene, calcitonin, and denosumab. One anabolic agent, teriparatide (see Medication), is available as well. Surgical care includes vertebroplasty and kyphoplasty (see Treatment). Osteoporosis is a preventable disease that can result in devastating physical, psychosocial, and economic consequences. Prevention and recognition of the secondary causes of osteoporosis are first-line measures to lessen the impact of this condition (see the images below).

WHO definition of osteoporosis

Bone mineral density (BMD) in a patient is related to peak bone mass and, subsequently, bone loss. Whereas the Tscore is the patients bone density compared with the BMD of control subjects who are at their peak BMD, the Z-score reflects a bone density compared with that of patients matched for age and sex. [7, 8, 9, 10] The World Health Organizations (WHO) definitions of osteoporosis based on BMD measurements in white women are summarized in Table 1, below.[9, 10] For each standard deviation (SD) reduction in BMD, the relative fracture risk is increased 1.5-3 times. The WHO definition applies to postmenopausal women and men aged 50 years or older. Although these definitions are necessary to establish the prevalence of osteoporosis, they should not be used as the sole determinant of treatment

decisions. This diagnostic classification should not be applied to premenopausal women, men younger than 50 years, or children. Table 1. WHO Definition of Osteoporosis Based on BMD Measurements by DXA(Open Table in a new window)
Definition Normal Low bone mass (osteopenia) Osteoporosis Severe or established osteoporosis Bone Mass Density Measurement BMD within 1 SD of the mean bone density for young adult women BMD 12.5 SD below the mean for young-adult women BMD 2.5 SD below the normal mean for young-adult women BMD 2.5 SD below the normal mean for young-adult women in a patient who has already experienced 1 fractures T-Score T-score 1 T-score between 1 and 2.5 T-score 2.5 T-score 2.5 (with fragility fracture[s])

BMD = bone mass density; DXA = dual x-ray absorptiometry; SD = standard deviation; T-score = a measurement expressed in SD units from a given mean that is equal to a patient's BMD measured by DXA minus the value in a young healthy person, divided by the SD measurement in the population. [18]

Z-scores should be used in premenopausal women, men younger than 50 years, and children. Z-scores adjusted for ethnicity or race should be used, with Z-scores of 2.0 or lower defined as "below the expected range for age" and with Zscores above 2.0 being defined as "within the expected range for age." The diagnosis of osteoporosis in these groups should not be based on densitometric criteria alone.

Alterations in bone formation and resorption

The hallmark of osteoporosis is a reduction in skeletal mass caused by an imbalance between bone resorption and bone formation. Under physiologic conditions, bone formation and resorption are in a fair balance. A change in either that is, increased bone resorption or decreased bone formationmay result in osteoporosis. Osteoporosis can be caused both by a failure to build bone and reach peak bone mass as a young adult and by bone loss later in life. Accelerated bone loss can be affected by hormonal status, as occurs in perimenopausal women; can impact elderly men and women; and can be secondary to various disease states and medications. Aging and loss of gonadal function are the 2 most important factors contributing to the development of osteoporosis. Studies have shown that bone loss in women accelerates rapidly in the first years after menopause. The lack of gonadal hormones is thought to up-regulate osteoclast progenitor cells. Estrogen deficiency leads to increased expression of RANKL by osteoblasts and decreased release of OPG; increased RANKL results in recruitment of higher numbers of preosteoclasts as well as increased activity, vigor, and lifespan of mature osteoclasts. Estrogen deficiency Estrogen deficiency not only accelerates bone loss in postmenopausal women but also plays a role in bone loss in men. Estrogen deficiency can lead to excessive bone resorption accompanied by inadequate bone formation. Osteoblasts, osteocytes, and osteoclasts all express estrogen receptors. In addition, estrogen affects bones indirectly through cytokines and local growth factors. The estrogen-replete state may enhance osteoclast apoptosis via increased production of transforming growth factor (TGF)beta. In the absence of estrogen, T cells promote osteoclast recruitment, differentiation, and prolonged survival via IL-1, IL-6, and tumor necrosis factor (TNF)alpha. A murine study, in which either the mice's ovaries were removed or sham operations were performed, found that IL-6 and granulocyte-macrophage CFU levels were much higher in the ovariectomized mice.[23] This finding provided evidence that estrogen inhibits IL-6 secretion and that IL-6 contributes to the recruitment of osteoclasts from the monocyte cell line, thus contributing to osteoporosis. IL-1 has also been shown to be involved in the production of osteoclasts. The production of IL-1 is increased in bone marrow mononuclear cells from ovariectomized rats. Administering IL-1 receptor antagonist to these animals prevents the late stages of bone loss induced by the loss of ovarian function, but it does not prevent the early stages of bone loss. The increase in the IL-1 in the bone marrow does not appear to be a triggered event but, rather, a result of removal of the inhibitory effect of sex steroids on IL-6 and other genes directly regulated by sex steroids. T cells also inhibit osteoblast differentiation and activity and cause premature apoptosis of osteoblasts through cytokines such as IL-7. Finally, estrogen deficiency sensitizes bone to the effects of parathyroid hormone (PTH). Aging In contrast to postmenopausal bone loss, which is associated with excessive osteoclast activity, the bone loss that accompanies aging is associated with a progressive decline in the supply of osteoblasts in proportion to the demand. This

demand is ultimately determined by the frequency with which new multicellular units are created and new cycles of remodeling are initiated. After the third decade of life, bone resorption exceeds bone formation and leads to osteopenia and, in severe situations, osteoporosis. Women lose 30-40% of their cortical bone and 50% of their trabecular bone over their lifetime, as opposed to men, who lose 15-20% of their cortical bone and 25-30% of trabecular bone. Calcium deficiency Calcium, vitamin D, and PTH help maintain bone homeostasis. Insufficient dietary calcium or impaired intestinal absorption of calcium due to aging or disease can lead to secondary hyperparathyroidism. PTH is secreted in response to low serum calcium levels. It increases calcium resorption from bone, decreases renal calcium excretion, and increases renal production of 1,25-dihydroxyvitamin D (1,25[OH]2 D)an active hormonal form of vitamin D that optimizes calcium and phosphorus absorption, inhibits PTH synthesis, and plays a minor role in bone resorption. Vitamin D deficiency Vitamin D deficiency can result in secondary hyperparathyroidism via decreased intestinal calcium absorption. Interestingly, the effects of PTH and 1,25[OH]2 D on bone are mediated via binding to osteoblasts and stimulating the RANKL/RANK pathway. Osteoclasts do not have receptors for PTH or 1,25[OH]2 D.[19] Osteoporotic fractures Osteoporotic fractures represent the clinical significance of these derangements in bone. They can result both from lowenergy trauma, such as falls from a sitting or standing position, and from high-energy trauma, such as a pedestrian struck in a motor vehicle accident. Fragility fractures, which occur secondary to low-energy trauma, are characteristic of osteoporosis. Fractures occur when bones fall under excess stress. Nearly all hip fractures are related to falls. [24] The frequency and direction of falls can influence the likelihood and severity of fractures. The risk of falling may be amplified by neuromuscular impairment due to vitamin D deficiency with secondary hyperparathyroidism or corticosteroids. Vertebral bodies are composed primarily of cancellous bone with interconnected horizontal and vertical trabeculae. Osteoporosis not only reduces bone mass in vertebrae but also decreases interconnectivity in their internal scaffolding.[19]Therefore, minor loads can lead to vertebral compression fractures. An understanding of the biomechanics of bone provides greater appreciation as to why bone may be susceptible to an increased risk of fracture. When vertical loads are placed on bone, such as tibial and femoral metaphyses and vertebral bodies, a substantial amount of bony strength is derived from the horizontal trabecular cross-bracing system. This system of horizontal cross-bracing trabeculae assists in supporting the vertical elements, thus limiting lateral bowing and fractures that may occur with vertical loading. Disruption of such trabecular connections is known to occur preferentially in patients with osteoporosis, particularly in postmenopausal women, making females more at risk than males for vertebral compression fractures (see the images below). Rosen and Tenenhouse studied the unsupported trabeculae and their susceptibility to fracture within each vertebral body and found an extraordinarily high prevalence of trabecular fracture callus sites within vertebral bodies examined at autopsy, typically 200-450 healing or healed fractures per vertebral body.[25]These horizontal trabecular fractures are asymptomatic, and their accumulation reflects the impact of lost trabecular bone and greatly weakens the cancellous structure of the vertebral body. The reason for preferential osteoclastic severance of horizontal trabeculae is unknown. Some authors have attributed this phenomenon to overaggressive osteoclastic resorption. Osteoporosis versus osteomalacia Osteoporosis may be confused with osteomalacia. The normal human skeleton is composed of a mineral component, calcium hydroxyapatite (60%), and organic material, mainly collagen (40%). In osteoporosis, the bones are porous and brittle, whereas in osteomalacia, the bones are soft. This difference in bone consistency is related to the mineral-toorganic material ratio. In osteoporosis, the mineral-to-collagen ratio is within the reference range, whereas in osteomalacia, the proportion of mineral composition is reduced relative to organic material content. Additional factors and conditions Endocrinologic conditions or medications that lead to bone loss (eg, glucocorticoids) can cause osteoporosis. Corticosteroids inhibit osteoblast function and enhance osteoblast apoptosis. [26] Polymorphisms of IL-1, IL-6 and TNFalpha, as well as their receptors, have been found to influence bone mass. Other factors implicated in the pathogenesis of osteoporosis include polymorphisms in the vitamin D receptor; alterations in insulin-like growth factor-1, bone morphogenic protein, prostaglandin E2, nitrous oxide, and leukotrienes; collagen abnormalities; and leptin-related adrenergic signaling.[20]

Epigenetics
Prenatal and postnatal factors contribute to adult bone mass. In one study, the health of the mother in pregnancy, the infants birth weight, and the childs weight at age 1 year were predictive of adult bone mass in the seventh decade for men and women.[27] It is postulated that growth in the first year of life programs growth hormone that is maintained into the seventh decade.[28] Larger babies and rapid growth in the first year of life predicted increased bone mass in adults aged 65-75 years.

Etiology
Osteoporosis has been divided into several classifications according to etiology and localization in the skeleton. Osteoporosis is initially divided into localized and generalized categories, and these 2 main categories are further classified further into primary and secondary osteoporosis. Postmenopausal osteoporosis (PMO) is primarily due to estrogen deficiency, senile osteoporosis is primarily due to an aging skeleton and calcium deficiency.

Primary osteoporosis
Patients are said to have primary osteoporosis when a secondary cause of osteoporosis cannot be identified, including juvenile and idiopathic osteoporosis. Idiopathic osteoporosis can be further subdivided into postmenopausal (type I) and age-associated or senile (type II) osteoporosis, as described in Table 2, below. Table 2. Types of Primary Osteoporosis (Open Table in a new window)
Type of Primary Osteoporosis Juvenile osteoporosis Characteristics

Usually occurs in children or young adults of both sexes Normal gonadal function Age of onset: usually 8-14 years Hallmark characteristic: abrupt bone pain and/or a fracture following trauma

Idiopathic osteoporosis

Postmenopausal osteoporosis (type I osteoporosis)

Occurs in women aged 50-65 years Characterized by a phase of accelerated bone loss, primarily from trabecular bone Fractures of the distal forearm and vertebral bodies common Occurs in women and men older than 70 years Represents bone loss associated with aging Fractures occur in cortical and trabecular bone Wrist, vertebral, and hip fractures often seen in patients with type II osteoporosis

Age-associated or senile osteoporosis (type II osteoporosis)

Secondary osteoporosis
Secondary osteoporosis occurs when an underlying disease, deficiency, or drug causes osteoporosis (see Table 3, below). Up to one third of postmenopausal women, as well as many men and premenopausal women, have a coexisting cause of bone loss,[29, 30] of which renal hypercalciuria is one of the most important secondary causes of osteoporosis and treatable with thiazide diuretics.[31] Table 3. Causes of Secondary Osteoporosis in Adults (Open Table in a new window)
Cause Genetic/congenital Examples

Renal hypercalciuria one of the most important secondary causes of osteoporosis; can be treated with thiazide diuretics Cystic fibrosis Ehlers-Danlos syndrome Glycogen storage disease Gaucher disease Marfan syndrome Menkes steely hair syndrome Riley-Day syndrome Osteogenesis imperfecta Hemochromatosis Homocystinuria Hypophosphatasia Idiopathic hypercalciuria Porphyria Hypogonadal states Androgen insensitivity

Hypogonadal states


Endocrine disorders[32]

Anorexia nervosa/bulimia nervosa Female athlete triad Hyperprolactinemia Panhypopituitarism Premature menopause Turner syndrome Klinefelter syndrome Cushing syndrome Diabetes mellitus Acromegaly Adrenal insufficiency Estrogen deficiency Hyperparathyroidism Hyperthyroidism Hypogonadism Pregnancy Prolactinoma Calcium deficiency Magnesium deficiency Protein deficiency Vitamin D deficiency[32, 33] Bariatric surgery Celiac disease Gastrectomy Malabsorption Malnutrition Parenteral nutrition Primary biliary cirrhosis Inflammatory bowel disease Ankylosing spondylitis Rheumatoid arthritis Systemic lupus erythematosus Hemochromatosis Hemophilia Leukemia Lymphoma Multiple myeloma Sickle cell anemia Systemic mastocytosis Thalassemia Metastatic disease Anticonvulsants: phenytoin, barbiturates, carbamazepine (these agents are associated with treatment-induced vitamin D deficiency) Antipsychotic drugs Antiretroviral drugs Aromatase inhibitors: exemestane, anastrozole Chemotherapeutic/transplant drugs: cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, high-dose methotrexate[34] Furosemide Glucocorticoids and corticotropin[35] : prednisone (5 mg/day for 3 mo)[36] Heparin (long term) Hormonal/endocrine therapies: gonadotropin-releasing hormone (GnRH) agonists, luteinizing hormone-releasing hormone (LHRH) analogues, depomedroxyprogesterone, excessive thyroxine Lithium Selective serotonin reuptake inhibitors (SSRIs) Alcoholism Amyloidosis Chronic metabolic acidosis Congestive heart failure Depression Emphysema Chronic or end-stage renal disease Chronic liver disease HIV/AIDS Idiopathic scoliosis

Deficiency states

Inflammatory diseases

Hematologic and neoplastic disorders

Medications

Miscellaneous

Immobility Multiple sclerosis Ochronosis Organ transplantation Pregnancy/lactation Sarcoidosis Weightlessness

The Effects of Smoking on Bone Health

Tips to help you quit smoking.
WebMD Feature Archive SMOKING AND OSTEOPOROSIS Whatever your age, the effects of smoking on bone health can't be ignored. The years from childhood until age 30 are prime time for building bone mass. "If an adolescent is smoking, they will not develop maximum bone mass. They will end up with a smaller skeleton and less bone mass, compared to a nonsmoker," says Primal Kaur, MD, an osteoporosis specialist at Temple University Health System in Philadelphia. Smoking continues to affect bone health in your 40s and 50s. Women that age begin to lose estrogen, which is very important for bones. If you smoke, bone loss is more rapid -- and with more complications, Kaur tells WebMD. Why Is Smoking So Damaging to Bone Health? "Nicotine and toxins in cigarettes affect bone health from many angles," Kaur says. Cigarette smoke generates huge amounts of free radicals -- molecules that attack and overwhelm the body's natural defenses. The result is a chain-reaction of damage throughout the body -- including cells, organs, and hormones involved in keeping bones healthy. The toxins upset the balance of hormones (like estrogen) that bones need to stay strong. Your liver produces more estrogen-destroying enzymes, which also leads to bone loss, says Kaur. "Smoking makes bone loss even worse in the menopausal years. It adds to the bone loss that's already occurring." Smoking triggers other bone-damaging changes, such as increased levels of the hormone cortisol, which leads to bone breakdown, says Kaur. "Research also suggests that smoking impedes the hormone calcitonin, which helps build bones - so that hormone can't do its job." There's more: "Nicotine and free radicals kill the osteoblasts -- the bone-making cells," she explains. "Smoking also damages blood vessels, so there is poor blood supply of oxygen. People who smoke have repeated fractures. Studies show that when a smoker suffers a fracture, they don't heal very well because of poor blood supply." Because smoking damages blood vessels, it also damages nerves in toes and feet, which can lead to more falls and fractures. "Smokers have double the risk of having a fracture. Heavy smokers increase the risk of fracture even more," Kaur says. If You Quit Smoking, Is It Possible to Improve Bone Health? "Bone building is a slow process, and it takes a long time to fix the damage, so some of the damage may be irreversible," Kaur says. "The heavier the smoker, the longer it will take to recover." But there is hope. She points to one recent study, published in 2006 in the Journal of Women's Health: After one year without smoking, a group of postmenopausal women had improved bone density, compared with women who continued smoking.