A Patient's Guide to Osteoporosis

Introduction
When people age - particularly women -- there often comes a loss
of height and weight, and the development of stooped posture. A
bone-thinning disease called osteoporosis often causes these
body changes. This disease is characterized by loss of bone
mass and structural deterioration of bone tissue, which leads to
bone fragility and increased susceptibility to fractures of the spine,
hip, and wrist. In fact, spinal fractures are the most common type
of osteoporotic fractures that exist. Forty percent of all women will
have at least one by the time they are 80 years old. These
vertebral fractures can permanently alter the shape and strength
of the spine.
Loss of bone mass begins at around age 30. Although men can
be affected by osteoporosis, the typical sufferers are older
women, particularly those who are past menopause. Bone loss
becomes worse in women after menopause because of the
body's lack of estrogen.
When bones lose mass they tend to weaken and become fragile,
increasing the risk of fracture under stress or because of a fall -
particularly in the spine and hip. However, falls in elderly women
are often the result, rather than the cause, of fractures. In severe
cases of osteoporosis, the bones can fracture with any kind of
slight movement and patients are sometimes left bedridden.
Most women are likely to feel some effects of osteoporosis in their
lifetime, but the good news is that much can be done to reduce
and even prevent loss of bone mass and fractures. In fact, new
treatments for this disease are being discovered each year, and
you can actively work to decrease your chances of suffering the
effects of osteoporosis. The key is prevention and intervention.
This website will offer you valuable information about the
following:
 Causes of Osteoporosis

 Risk Factors for Osteoporosis

 Symptoms

 Diagnosis

 Treatment Options and Prevention

 Medications

Causes of Osteoporosis
Several causes and types of osteoporosis will be explained in this
section. The first is primary osteoporosis, which has two types - (I)
and (II). Type I is an excessive loss of the spongy tissue of the
bone (cancellous bone), with some sparing of outer bone. This
type of osteoporosis is six times more common in women than
men, and the onset usually occurs in the 15-20 years following
menopause. The loss of bone is thought to be linked to an
estrogen deficiency in women and a testosterone deficiency in
men - both of which are due to aging. In this type of osteoporosis,
vertebral spine fractures are the most common result.
Type II refers to a simultaneous loss of both the outer bone and
the spongy tissue inside the bone. This type is only two times
more common in women than men. It typically occurs once
people reach their 70s and 80s. It is also thought to be the result
of a deficiency in dietary calcium, age-related Vitamin D decline,
or increased activity of the parathyroid glands (secondary
hyperparathyroidism). Hip fractures are the most common result
of this type of osteoporosis.
Secondary osteoporosis, also known as "high-turnover
osteoporosis", is a condition of an increased rate of bone
remodeling - or an increase in the amount of bone being
remodeled. This condition causes an overall increase in the rate
of bone loss. Bone turnover is caused by two functions: (1) the
production of new bone, and (2) the loss (resorption) of old bone.
The amount of bone mass you have depends on the balance
between these functions, which is your bone turnover rate. If you
have a high turnover rate, you are at greater risk for developing
osteoporosis.
Secondary osteoporosis can also have four hormonal causes:
 Hyperparathyroidism - increased activity of the parathyroid glands

 Hyperthyroidism - an excessive secretion of the thyroid glands

 Diabetes - a disease where the body does not produce or use insulin correctly (This leads to:
hyperglycemia - an increase in blood sugar, increasing susceptibility to infection, and glycosuria -
glucose in the urine.)

 Hypercortisolism - a result of systemic illness or long-term use of oral corticosteroid

Osteoporosis can also be the result of disorders where the bone

marrow cavity expands at the expense of the trabecular bone.
The trabecular bones have a honeycomb appearance and large
marrow spaces. They are called cancellous or spongious bone,
and are found along lines of stress created by weight-bearing
forces. If a trabecular bone is affected by increased bone marrow
cavities, it loses some of its strength.
Other links to secondary osteoporosis are:
 Thalassemia - a hereditary form of anemia

 Multiple myeloma - multiple tumors within the bone and bone marrow

 Leukemia - a serious disease that is characterized by unrestrained growth of white blood cells in
the tissues

 Metastatic bone diseases - when malignant tumor cells spread from one part of the body to
another; the disease travels through the blood and settles in the bones

Risk Factors for Osteoporosis

Osteoporosis does not affect everyone. There are risk factors that
help predict your chances of developing it. Some risk factors are
simply genetic, meaning you inherited them from your biological
parents. Some risks are due to medical factors that you may not
be able to avoid, such as use of particular medications. Other
factors are lifestyle-related, meaning you have control over
reducing these risk factors.
The highest biological and medical risk factors are:
 Biological Sex - Women have a greater chance of developing osteoporosis.

 Race - Caucasians and Asians are most likely to suffer this extensive bone loss.
 Age - Since bone loss begins at around age 30, as you age your risk for osteoporosis increases.

 Family History - If others in your family have experienced hip or spine fractures or become hunched
over as they age, you are at greater risk of experiencing the same symptoms.

 Body Frame - A slight, thin body frame with a low body weight for height will increase the risk of
osteoporosis.

 Post Menopause - Women past menopause have reduced estrogen, so their chances of losing
bone mass increase.

 Low Estrogen - There is more risk if women have had a low rate of estrogen over their lifetime. The
deficiency can be the result of late onset of puberty/getting their period, early menopause (before
40), or an absence or suppression of menstruation.

 Medication Use - Certain medications increase the risk of osteoporosis because they contribute to
loss of bone mass when used long term; these drugs include steroids, inhaled steroids,
antiepileptic drugs, immunosuppressants, anticoagulants, and thyroid hormone suppressive
therapy.

 Nutritional Conditions - Conditions such as anorexia nervosa, chronic liver disease, malabsorption
syndromes, or malnutrition can increase the risk of osteoporosis.

 Endocrine Disease or Metabolic Causes - These could include thalassemia, diabetes, or

hemochromatosis.

 Other Medical Disorders - These include: Down's syndrome, mastocytosis, myeloma and some
cancers, renal tubular acidosis, rheumatologic disorders, and immobilization.

Lifestyle risk factors that lead to bone loss include:

 Low Calcium Intake - Consumption below 300 mg per day (which is equal to one glass of milk) is
considered low.

 Low (or no) Vitamin D in Your Diet - Vitamin D comes from sunlight and foods such as egg yolks,
fortified milk and cereals, and some types of fish.

 High Caffeine Intake - More than two to three cups of caffeinated coffee each day is considered
high if you have a low calcium intake.

 Tobacco use - This includes current use as well as past use of tobacco.

 Alcohol use - More than 7 oz. of alcohol per week can slightly increase the risk of hip fractures.

 Low Activity - Your activity rate is considered low if you do not walk or exercise regularly.

Symptoms
Perhaps the most common symptom of osteoporosis is a
vertebral compression fracture or hip fracture. The compression
fractures in the spine, caused by weakened vertebrae can lead to
pain in your mid-back area. The fractures often stabilize on their
own and the pain goes away, but sometimes the pain persists
because the crushed bone continues to move around and break.
In severe cases of osteoporosis, actions as simple as bending
forward can be enough to cause a "crush fracture", or spinal
compression fracture. These vertebral fractures cause loss of
height and a humped back. This disorder (kyphosis or a
"dowager's hump") is an exaggeration of your spine that causes
the shoulders to slump forward and the top of your back to look
enlarged and humped.
Diagnosis
If you have symptoms of osteoporosis, you should consult with
your doctor. Additionally, older women should discuss their risks
of osteoporosis with a health care provider, even if they are not
currently exhibiting any signs of the disorder. All women should
be aware of the many preventative steps to take to decrease the
risk of developing osteoporosis.
To diagnosis osteoporosis, your physician can do several things.
Diagnosis will begin with a physical examination that measures
height, weight, and middle fingertip-to-middle fingertip arm span.
This gives a rough estimate of what your original height might
have been in young adult life. Vertebral tenderness will also be
checked.
After a physical, laboratory tests, and bone mineral density might
be performed. First is bone densitometry, which reports the
density of your bone mass. This test is not part of routine
screening, but will be done if osteoporosis is suspected or if you
are at high risk for the disease.
As for laboratory tests, the following are conducted to rule out any
secondary disorders that might be causing the osteoporosis.
There is testing of urine and serum to look for concentrations of
calcium, serum protein, inorganic phosphorus, alkaline
phosphates, or CBC. These tests are done to exclude the
presence of another disease that may be the cause of secondary
osteoporosis. Biochemical measures of bone turnover can also be
looked at along with other clinical information to evaluate risk of
osteoporosis. A complete blood cell count, with a separate white
cell count, can be taken to rule out other diseases. In elderly
people, thyroid function tests, serum, and urinary protein
electrophoresis should be taken to rule out hyperthyroidism and
multiple myeloma.
X-rays might be taken if your bone mass is suspected to be 30%-
50%. If bone loss is not thought to be this high, X-rays are not
beneficial in determining osteoporosis.
Treatment Options and Prevention
Though there is no cure for osteoporosis, in recent years many
effective treatments and prevention plans have been discovered.
The most common are listed below:
Calcium
The most fundamental suggestion is to increase your calcium
intake, either through dietary changes or supplemental pills. It is
best for people to begin adequate calcium intake at an early age,
as bone mass begins to decrease around the age of 30. After age
30, calcium helps decrease bone loss, strengthen bones, and
decrease the risk of fractures. The recommended daily intake for
women, 25-50 years of age, and women over 50 who take
hormone replacements, is 1,000 mg per day. Women over 50
who do not take hormone replacements should have 1,500 mg
per day. Men 25-65 years should have 1,500 mg per day, and
men and women over 65 should have 1,500 mg per day. If you
take calcium supplements, make sure they contain Vitamin D, as
this helps with absorption. In addition, calcium citrate is better
absorbed than calcium carbonate, which has to be taken with
food.
Vitamin D
A vitamin D deficiency may contribute to bone loss and fracture,
and at least 800 mg per day is recommended for all adults. Many
calcium supplements contain vitamin D. You can also get vitamin
D through foods such as: egg yolks; fortified milk and cereals; and
fish, such as halibut, mackerel, sardines, shrimp, pink salmon,
and cod liver oil.
Exercise
Exercise five days a week for at least 30 minutes helps reduce
bone loss. The best exercises for maintaining bone mass are
weight-bearing exercises. This includes walking.
Medications
Currently, four medications have approval from the Food and
Drug Administration (FDA).
Hormone Replacement Therapy (HRT)
Hormone/estrogen replacement therapy is used for both
prevention and treatment of osteoporosis. HRT can reduce bone
loss, increase bone density in the spine and hip, and reduce the
risk of hip and spinal fractures in postmenopausal women.
HRT is usually given as a pill or skin patch. It is effective even
when started after age 70. However, when estrogen is taken
alone, it can increase the risk of developing endometrial cancer
(cancer of the uterine lining). For this reason, the hormone,
progestin, is usually prescribed in combination with estrogen for
women whose uterus is intact.
Side effects of HRT can include: nausea, bloating, breast
tenderness, and high blood pressure. Some studies indicate a
relationship between estrogen use and breast cancer, while other
studies do not. Please discuss the pros and cons of estrogen
replacement therapy with your health care provider.
Bisphosphonates
These compounds inhibit breakdown of bone and slow down
bone removal. They are also shown to increase bone density and
decrease the risk of fractures at both the hip and spine. The
bisphosphonate that has been approved by the FDA for
preventing and treating osteoporosis in postmenopausal women
is alendronate.
The strongest side effect of alendronate is gastrointestinal
problems. For this reason, it has to be taken on an empty
stomach. To minimize side effects, take it with a full glass of water
and remain in an upright position for at least one half hour after
taking the medication.
Calcitonin
This is used for women who cannot, or choose not to, take
estrogen. For women who are at least five years past
menopause, calcitonin can increase spinal bone density and slow
bone loss. Calcitonin is a protein, so it cannot be taken orally -
otherwise it would digest before it could work. Calcitonin is
available as an injection or nasal spray.
Selective Estrogen Receptor Modulators (SERMs)
These compounds have effects similar to estrogen in some parts
of the body, such as the spine and hip. SERMs seem to prevent
bone loss at the spine, hip, and total body. Raloxifene is the
SERM drug currently approved by the FDA for prevention of
osteoporosis. However, its impact on the spine does not appear
to be as powerful as either estrogen replacement therapy or
alendronate. There are no common side effects with raloxifene,
but sometimes women have experienced hot flashes and deep
vein thrombosis (DVT).
Summary
Remember that osteoporosis is a highly preventable and treatable
disease. If you are at risk for osteoporosis, please consult with
your health care provider to develop a prevention and treatment
plan.
Osteoporoza este cea mai frecventa boala osoasa a adultului. Afectiunea difera de osteomalacie si
rahitismprin faptul ca este rezultatul reducerii matricei organice osoase, si nu a unei mineralizari
osoase insuficiente. In osteoporoza, activitatea osteoblastica a osului este mai redusa decat cea
normala, , si, in consecinta, rata formarii osteoidului este scazuta. Ocazional insa, ca si in
hiperparatiroidism, cauza afectarii osoase este excesul activitatii osteoclastelor.

Scheletul este unul dintre cele mai mari organe sistemice, alcatuit dintr-o matrice minerala si o mare
unitate de remodelare celulara, formata din osteoblasti, osteoclasti osteocite si celule de sustinere.
Pe langa functia de sustinere, scheletul indeplineste rol si in depozitarea mineralelor, ajutand la
mentinerea normala a nivelelor de calciu si fosfat prin procese de remodelare osoasa si prin secretia
factorului de crestere fibroblastic – FGF23. De asemenea, reprezinta locul hematopoiezei,
reprezentand o nisa intre elementele osului trabecular-osteoblaste, adipocite, celule
reticuloendotelialem sinusoide si stroma mezenchimala, si celulele stem, intr-un mediu hipoxic.
Aceasta nisa ofera precursorii necesari repararii oricarei injurii de la nivelul organismului. De
asemenea, depoziteaza aprox 10-15%din cantitatea totala de tesut adipos a organismului.

MATRICEA OSOASA

Matricea osoasa este formata din fibre de colagen de tip I dispuse in straturi cu diverse orientari.
Matricea contine cateva proteine in plus, inclusiv alte tipuri de colagen care au rolul de a interveni in
interactiunea dintre fibrele de colagen de tip I si fibrele non-colagenoase. Proteinele non-
colagenoase, ca osteocalcina si cativa proteoglicani, reprezinta aprox 10% din totalul proteinelor din
os si dicteaza orientarea fibrelor, mineralizarea osului, regkeaza atasamentul celulelor osoase la
matrice si joaca un rol in procesul de formare-resorbtie osoasa.

Proteinele din compozitia matricei variaza, de la cele cu greutate mare (cu rol in atasare), precum
thrombospondin si fibronectina, la cele cu greutate moleculara mica, proteine gamma-carboxilate
dependente de vitamina K, PRECUM PROTEINA Gla si osteocalcina, proteine care leaga calciul.
Osteocalcina poate fi incomplet sau total carboxilata, in functie de numarul de sit-uri de acid glutamic
din structura moleculei, care sunt transformate in acid glutamic de catre enzime dependente de
vitamina K. Carboxilarea gamma incompleta poate fi o consecinta a tratamentului cu warfarina.

Osteocalcina sub-carboxilata GLU13-OCN este eliberata din matricea scheletala in timpul resorbtiei
osoase.

Unele proteine non-colagenice sunt foarte acide si joaca un important rol atat in semnalizare, cat si
in hematopoieza, fiind glicoproteine sau proteoglicani, inalt fosforilate, caracteristica ce le permite sa
se lege de calciu.

In studii efectuate pe soareci, a fost demonstrat faptul ca mutatii la nivelul genei osteonectinei duc la
osteopenie, pe cand deletii la nivelul genei osteocalcinei determina cresterea masei osoase.

Mineralizarea osoasa este realizata prin formarea de cristale de hidroxiapatita, alcatuite din
carbonat, magneziu, sodiu, potasiu, calciu si fosfat. Mineralizarea se realizeaza pe doua cai:
extracelular, catalizata prin fosfataza alkalina, si in interiorul veziculelor de la nivelul matricei,
accelerata de enzima phospho1. Procesul de mineralizare necesita calciu, fosfat si fosfataza alkalina,
si este alterat in cazul deficientei de vitamina D, deficientei de calciu, hipofosfatemie, mutatii ale
genei care codifica fosfataza alkalina. Cea mai dramatica lipsa de mineralizare poate fi intalnita in
sindromul de hipofosfataza, in care fosfataza alkalina este absenta.

In procesul de remodelare osoasa, colagenul este clivat si degradat de catre colagenoze la un pH

neutru. Exista 3 forme de colagenoze, dintre care osteoblastul uman exprima genele pentru
colagenozele 1 si 3. Studii recente au demonstrate ca si osteocitele participa la procesul de
remodelare. Osteocitele reprezinta osteoblasti diferentiati terminal care poseda receptori pentru
PTH si au activitate metabolica. Aceste cellule se organizeaza sub o unitate functionala numita
osteon. Osteocitele sunt o sursa bogata de RANKL, care stimuleaza diferentierea osteoclastelor,, in
special in situatiile in care necesarul de calciu e mare, ca in lactatie sau imediat dupa statusul de
hipoestrogenism. Mai mult, osteocitele pot secreta enzyme care degradeaza matricea osoasa in
procesul de osteoliza osteocitica, prin secretia de fosfataza acida si colagenoze.

Osteoblastii deriva din celulele mezenchimale ale scheletului si sunt cellule differentiate care nu se
mai supun mitozei, secretand collagen siproteine non-colagenice. De exemplu, osteocalcina este
sintetizata aproape numai de osteoblasi si osteocyte, si in mare proportie este depozitata si se
elibereaza treptat in procesul de remodelare, fapt pentru care este un marker al turn-over-ului osos
si nu al formarii osose per se.

Celulee osteoblastice sunt importante in formarea osoasa si in initierea resorbtiei osoase. Atat
osteoblastii mature,cat si osteocitele au rol in activarea resorbtiei. Factorii hormonali care activeaza
resorbtia osoasa isi desfasoara activitatea prin intermediul osteoblastelor., stimuland sinteza si
eliberarea RANKL si factorul de stimulare colonial 1, esentiale in osteoclastogeneza. Osteoblastii
produc factori aditionali care regleaza resorbtia osoasa, printer care cytokine, prostaglandine si
factori locali de crestere. De asemenea, osteoblatsi au rol si n initierea resorbtiei osoase prin
eliberarea de colagenoze, metaloproteinaze si activatori ai plasminogenului.

Osteoclastele deriva din progenitorii hematopoietici, sub influenta 1,25-dihidroxivitamina D,

prostaglandine, IL-1, IL-6 si TNF. Principalul stimulator al formarii osteoclastelor este RANKL, un
membru al superfamiliei TNF. Acest produs a fost initial recunoscuta ca fiind secretata de limfocitele
T activate, dar reprezinta si un stimulator al osteoclastogenezei din celulele stromale mezenchimale,
preosteoblasti, osteocyte si condrocite hipertrofice. Productia RANKL in linia osteoblastica este
stimulate de catre toti agentii care stimuleaza formarea osteoclastelor, inclusive PTH, 1,25(OH)2D,
prostaglandine si multe cytokine. Soarecii care au RANKL deficitar nu pot forma osteoclaste si au
OSTEOPEROSIS.

OPG este un inhibitor native al osteoclastogenezei, este un receptor solubil al RANKL care impiedica
interactiunile dintre RANKL si RANK. Produsii de stimulare ai resorbtiei osoase, ca PTH, 1,25-oh2-d si
prostaglandina E2 inhiba productia de OPG (deficient de OPG=osteoporoza).

Receptorul active al RANKL este RANK, membru al familiei TNF. Osteoclastele si precursorii exprima
RANK.

REMODELAREA OSOASA

Masa osoasa adulta este determinate de doua procese: acizitia de masa osoasa din timpul
adolescentei si pierderea de masa osoasa din timpul maturitatii. Cele mai vulnerabile perioade in
cazul femeilor sunt in timpul perioadei de crestere accelerate lineara din adolescent (10-16 ani) si
imediat dupa menopauza (45-60) de ani.In cazul barbatilor, pierderea de masa osoasa este mai
gradual.

Ciclul de remodelare are la baza resorbtia osoasa la aceeasi rata cu formarea de masa osoasa.

Remodelarea osoasa include osteoclast, osteoblast, osteocit, si cellule de sustinere. Maduva osoasa
include pe cele de sus, plus elemente hematopoietice, adipocyte, cellule reticuloendoteliale, si cellule
mezenchimale. Precesul de remodelare este ma pronuntat in oasele trabeculare (coloana, femur
proximal, calcaneu), pentru ca ele sunt compartimentul cel mai active metabolic din schelet,
elementele trabeculare fiind inundate de capilaritate si macrophage locale.

Remodelarea osoasa incepe cu activarea osteoblastelor latent de pe suprafata oaselor, cat si

activarea celulelor de sustinere. Stimulul remodelarii poate fi reprezentat de microleziuni sau
schimbarile de forta locale resimtite de catre osteocyte, desi e posibil ca factorii locali secretati de
catre osteoblaste, osteoclaste sau cellule de sustinere sa fie implicate in initiere. Aceste interactiuni
intercelulare semnalieaza recrutarea si diferentierea celulelor multinucleate din celulele stem
hematopoietice. Dupa inducerea resorbtiei de catre osteoclaste component ale matricei ca TGF-
BETA, IGF-1, collagen, osteocalcina, calciu si alte component preteine si inerale, sunt eliberate local.
La adultii sanatosi

OSTEOPOROZA SECUNDARA

Osteoporoza secundara este definite ca pierderea de masa osoasa, alterari ale microarhitecturii
osoase si prezenta fracturilor de fragilitate, secundare unei patologii de baza sau unei medicatii.
Osteoporoza secundara ramane o provocare din punctual de vedere al diagnosticului si
tratamentului, fiind destul de frecventa, in special la pacientele in premenopauza si populatia tanara,
la cere screeningul de osteoporoza nu se realizeaza. In plus, patologiile de baza sunt diverse si rare,
necesitand teste specific de diagnostic, terapia nedand rezultate daca nu se recunosc patologile de
baza. De exemplu, alendronatul a aratat o eficacitate redusa la femeile cu osteoporoza postclimax si
in tratament cu levo-thiroxina dupa cancerul tiroidian diferentiat. In plus, eficacitatea anti-fractura a
terapiilor nu a fost clar demonstrate, cu exceptia osteoporozei induse de glucocorticoizi si in
osteoporoza sec hipogonadismului la barbate, iar utilizarea medicatiei anti-osteoporotice se bazeaza
pe DMO.

MECANISM DE APARITIE A OSTEOPOROZEI SECUNDARE

1. BOLI ENDOCRINE.

1.1. EXCES DE GLUCOCORTICOIZI – fie ca e vorba despre exces endogen, fie ca urmare a administrarii
exogene, GCafecteaza structura normal a scheletului prin diverse efecte celulare, dintre care
inhibarea formarii osoase prin inducerea apoptozei osteoblastelor si steocitelor este cea mai critica.
Pierderea de masa osoasa predominant vertebrala, cu prezenta de fracture sunt caracteristice,
precum si riscul mare de carede secundar atrofiei musculare induse de GC si alterarea functiei
neuromusculare. Chiar si dozele mici de GC (2.5-7.5 mg prednisolone/zi) sunt associate cu un risc
crescut de 2.6 ori de fractura vertebrala, pe cand dozele mai mari de 7.5 mg/zi se asociaza cu un risc
crescut de 5 ori. In bolile reumatologice, pierderea rapida de masa osoasa si riscul crescut de fracture
sunt consecutive statusului pro-inflamator citokinic si mediului imunosupresat.

1.2. HIPERTIROIDISM – impactul hipertitoidismului ca factor de risc de fractura a fost stabilit print-un
studiu larg de 686 femei la postclimax cu TSH supresat sub 0.1 mUI/l, care a fost considerat ca risc de
4-5 ori mai mare pentru fractura de sold si de coloana. O meta-aaliza care a inclus 21 de studii a
indicat ca terapia hormonala de supresie a TSH-ului in cancerul tiroidian diferentiat, cu hipertiroidism
subclinic, este asociat cu osteoporoz la pacientele postmenopauza. Bazat pe modelul animal, atat
excesul de hormoni tiroidieni, cat si supresia TSH – uluiau fost implicate. Activarea receptorului alfa a
hormonilor tiroidieni pe osteoblaste si osteocite are ca rezultat resorbtia osoasa si pierderea de masa
ososa.

1.3. HIPERPARATIROIDISMUL PRIMAR – excesul cronic de PTHare efect catabolic la nivelul

scheletului, si afecteaza in special osul cortical, decat pe cel spongios, de aceea pierderea de masa
osoasa este predominanta la nivelul treimei medii a antebratului si la nivelul capului femural, coloana
vertebrala fiind mai putin afectata (fiind predominant din os spongios construita). In cazul pacientilor
asimptomatici, care prezinta frcatura de fragilitate sau scor T<-2.5, prezinta indicatie de
paratiroidectomie. Un studiu observational efectuat pe parcursul a 15 ani a demonstrat faptul ca
paratiroidectomia a normalizat indicatorii biochimici ai turn-over-ului osos si a prezervat DMO, pe
cand pacientii la care interventia nu a fost efectuata au avut pierdere din masa corticala osoasa.

1.4. HIPOGONADISMUL MASCULIN – androgenii sunt cruciali in achizitionarea peak-ului de masa

osoasa si in mentinerea fortei osoase. Efectul androgenilor la nivel osos e posibil sa fie mediat d catre
estrogeni. Hipogonadismul determina cresterea remodelarii osoase cu pierdere osoasa rapida.
Deprivarea de andogeni prin tratament cu agonisti de GnRH in cancerul de prostata reprezinta un risc
major de osteoporoza.

1.5. – OSTEOPOROZA DIN SARCINA – mecanismul este putin elucidat, fiind incriminate deficitul de
vitamina D, consumul redul de produse bogate in calciu si proteine, masa osoasa redusa, cresterea
proteinelor legate de PTH, cresterea turn-over-ului osos. Sarcinili multiple sau perioadele lungi de
lactatie nu se asociaza cu osteoporoza. Femeile insarcinate sunltla risc de a dezvolta osteoporoza
daca asociaza patologii tromboembolice care necesita tratament cu heparine.

1.6. OSTEOPOROZA DIN DZ TIP 1 – riscul de fractura de fragilitate este de 12 ori mai mare la pacientii
cu diabet zaharat de tip 1. DMO scae secundar lipsei de actiune a hormonului anabolic insulina si a
altor proteine beta celulare, precum amilina. Complicatiile diabetice, precum retinopatia,
polineuropatia si nefropatia reprezinta factorii principali ai scaderii DMO si cresterii riscului de
fractura, in special pentru ca acestea cresc riscl de cadere.

1.7. DEFICITUL DE GH- IGF-1 si proteinele de legare ale IGF-1, produse dupa stimularea receptorilor
de la nivel hepatic de catre GH, reprezinta un stimulator pentru functia osteoblastica si formarea
osoasa. Pacienti cu deficit de GH netratat au un risc crescut de 3 ori de fracturi osteoporotice, iar
gradul de osteopenie se coreleaza cu durata expunerii la deficit, dar masurarea cu exactitate a DMO
la acesti pacienti este dificila din cauza staturii mici, si simplicit, a dimensiunilor mici ale oaselor.

2. BOLI GASTROINTESTINALE

2.1. BOALA CELIACA – diareea cronica si malabsorbtia secundare atrofiei vilozitatilor intestiale sunt
caracteristice bolii celiace, c laterarea absorbtiei calciului si deficientei de vitamina D, rezultand in
osteomalacie si hiperparatiroidism secundar. Un studiu a demonstrat ca pacientii cu osteoporoza
sunt de 17 ori mai predispusi la a dezvolta boala celiaca, fapt pentru care se impune test seroloic de
screening la toti pacientii cu osteoporoza pentru boala celiaca.

2.2. BOLI INFLAMATORII INTESTINALE – statusul pro-inflamato cronic, diareea, asociata sau nu cu
malabsorbtia, IMC scazut si terapia cronica sau intermitenta cu GC reprezinta factorii principali care
duc la osteoporoza. In plus, deficitul de vitamina D la cei cu sindrom de intestin scurt sau cu
pierderea integritatii ileonului teminal (cu pierderea functionalitatii), spitalizarile repetate,
imobilizarea prelungita pot contribui la scaderea DMO.Sindromul de intestin scurt este factor de risc
pentru osteoporoza.

2.3. GASTRECTOMIE SI TERAPIE CRONICA CU IPP – dupa gastrectomie, osteoporoza se dezvolta pana
la o treime din pacienti si poate fi asociata cu absorbtia scazuta de calciu secundar cresterii pH-ului
gastrointestinal. In mod similar, perioadele crescute de uz de IPP cresc riscul de fracturi vertebrale de
3-5 ori la femeile postmenopauza. Pierderea acidului gastric altereaza absorbtia carbonatului de
calciu, comparativ cu gluconatul de calciu sau citratul de calciu, care se absorb independent de pH,
dar se folosesc mai putin.

2.4. CHIRURGIE BARIATRICA – pierderea osoasa dupa chirurgie bariatrica a devenit o provocare.
Variabilele proceduri de chirurgie bariatrica se asociaza cu scaderea absorbtiei fractionate a calciului
si cu deficit de vitamina D secundar malabsorbtiei. Pierderea de masa soase se coreleaza in acest caz
cu gradul de scadere ponderala, dublandu-se riscul de frractura dupa chirurgia bariatrica.

3. MIELOMUL SI MASTOCITOZA SISTEMICA –

3.1. MIELOMUL SI GAMAPATIA MONOCLONALA DE SEMNIFICATIE NEDETERMINATA – mai multe

legaturi celulare si umorale intre celulele mielomale si celulele osoase contribuie la osteoporoza,
afectand scheletul central. Celulele mielomale stimuleaza expresia RANKL si al altor factori pro-
osteoclastogenici, stimuland osteoclastogeneza si resorbtia osoasa.In plus, celulele mielomale
secreta dickkopf-1, un inhibitor solubil al semnalizarii Wnt, supresand diferentierea osteoblastelor.
Un studiu retrospectiv pe 165 de pacienti cu mielom a aratat faptul ca in anul precedent
diagnosticarii mielomului, au fost observate de 16 ori mai multe fracturi decat asteotate, dintre care
doua treimi fracturi patologice la nivel vertebral sau la nivelul coastelor, cu risc de fracura
osteoporotica crescut de 3 ori. 1 din 20 de pacienti diagnosticat cu osteoporoza prezinta mielom
multiplu sau gammapatie monoclonala d semnificatie nedeterminata.

3.2. MASTOCITOZA SISTEMICA – pierderea de masa osoasa poate fi rapida si severa, afectand atat
oasele lungi, cat si coloana vertebrala. Osteoporoza este secundara degranularii excesive a
mastocitelor, rezultand produsi precum IL-1, IL-3, IL-6 si histamine, care stimuleaza diferentierea
osteoclastelor din precursori. O mutatie activatoare a tirozin-kinazei, prezenta in peste 90% din
pacientii adulti cu mastocitoza, contribuie la cresterea resorbtiei osoase.

4. OSTEOPOROZA INDUSA DE HIV – pacientii cu HIV prezinta risc de fractura osteoporotica nu dar in
locurile de tesut spongios, ci si in alte regiuni. Osteoporoza este sec trata antiretroviral, IMC scazut,
hipogonadism, infectii si infalamtii, deficitului de vitamina D, deficitului de GH, tabagismului si
consumului de alcool.

5. OSTEOPOROZA INDUSA DE MEDICAMENTE – efectele edverse ale glucocorticoizilor si ale

inhibitorilor de calcineurina (ciclosporina A), cu rol imunosupresant, utilizate in bolile inflamatorii si
post-transplant

Utilizarea tiazolidindionelor – rosiglitazona si pioglitazona, agonisti ai PPAR-gama, se asociaza cu risc

crescut de 3-5 ori de fractura la humerus femur si sold la femei in postmenopauza. Aceste alterari pot
fi rezultatul suntarii

Deprivarea androgenica sau estrogenica, ca terapii in cancerul de prostata sau de san: terapiile de
deprivare androgenica include agonistii GnRH (goserelin, buserelin, leuprolide, triptorelin), care
cauzeaza hipogonadism hipogonadotropic, si anti-androgeni (bicalutamide si ciproteron acetat), care
blocheaza actiunea periferica a androgenilor. In mod similar, utilizarea inhibitorilor de aromataza ca
anastrozole, letrozole si exemestane,reduce conversia adrenala a androgenilor in estrogeni, cauzeaza
un turn-over osos rapid, care duce la pierderea de masa osoasa si fracturi de fragilitate.

DIAGNOSTIC

1. Istoric detaliat al factorilor clinici de fractura, patologii subiacente medicatie la domiciliu,

comportamente ca tabagism si consum de alcool. Riscul de cadere.

2. Examen clinic.

3. DXA – pt dg osteoporoza sec – CV si femur. – calcificarile aortice si osteofitele onteractioneaza cu

osteodensitometria la nivelul CV, fapt pentru care se realizeaza si la nivelul femurului. In cazul unei
patologii de baza, riscul de fractura este independent de DMO. De ex pacientii cu insuficienta renala
cronica pot avea fragilitate osoasa, in ciuda unei valori normale DMO. In plus, la pacienii cu terapie
GC, pragul pentr DMO este mai mare, astefel incat primesc medicatie in stadiul de osteopenie.
Radiografiile la nivelul CV ar trebui facute la cei cu dureri de spate, deformari recente ale coloanei,
pierdere de peste 3 cm in inaltime, pt detectarea fracturilor vertebrale, leziunilor osteolitice,
tumorilor, dar nu trebuie efectuate cu scopul de screening al osteoporozei.

4. Teste de laborator: functie renala, functie hepatica, HLG, calciu si fosfor serice, PCR, P-ALK, 25-OH-
VIT D TSH, TEST, PTH, elecroforeza proteinelor plasmatice, excretia urinara de calciu/24h, Ac anti-
transglutaminaza (b. celiaca, in special daca exista anemie carentiala I deficit de vitamina d); daca Ac
sunt pozitivi, pt dg bolii celiace ar trebui ulterior biopsie duodenala. Masurarea ritmului cortiolic si
efectuarea testului de supresie la dexametazona pentru sindrom Cushing. Pentru evaluarea
mastocitozei sistemice masurarea produsilor derivati (IL-1,3,6), triptaza sanguina, excretia urinara de
histamina din urina/24h (poate fi normala, deoarece histamina este termolabila), desi mai bine este
masurarea N-metilhistaminei sau a 11-beta-prostaglandinei F2alfa, mai specifice. Testarea genetica
COL 1A este necesara pentru diagnosticarea osteogenesis imperfecta, diagnosticata cel mai frecvent
pe baza unui istoric familiar pozitiv, fracturi recurente de fragilitate, sclerelor albastre, deficitului de
auz, necesitand rareori testare COL1A.

5. Biopsie din creasta iliaca – la pcientii la cere evaluarile anterioare sunt neconcludente, la pcienti
tineri cu fracturi multiple, la pcientii cu fracturi care apar sub tratament antiresorbtiv. Rolul este de a
distinge intre osteomalacie si osteoporoza, in dg mastocitozei, in evaluarea bolilor maligne
infiltrative.

6. Markerii ososi ai turn-over-ului sunt nespecifici in osteoporoza secundara, dar pot avea rol in
monitorizarea tratamentului.

TRATAMENT

OBIECTIVE: tratarea patologiei de baza si tratarea osteoporozei si prevenirea fracturilor viitoare.

Existand putine studii efectae pe osteoporoza secundara, ghidurile sunt bazate mai mult pe
experienta clinicienilor decat pe medicina bazata pe dovezi.

1. TRATAMENTUL BOLII DE BAZA

1.1. BOLI ENDOCRINE:

o Sindrom Cushing si hiperparatiroidism – chirurgical

o Hipertiroidism – endogen: ATS, radioiodoterapie, chirurgical
- Exogen: ajustare ATS
o Hipogonadism: daca exist a semne si simptome, deficitul trebuie corectat; reducerea riscului
de fractura pa barbatii care primesc tratament cu testosteron de sinteza nu a fost
demonstrata, dar crestere DMO a fost evidentiata.
o Terapie de substitutie cu GH- creste DMO, fara reducerea riscului de fractura
o Intensificarea insulinoterapiei in cazul pacientilor cu DZ – si prevenirea caderilor
o Anorexia nervoasa: cel mai bun tratament este reprezentat de alimentarea normala, intrucat
terapiile hormonale pe baza de estrogeni si tratamentul cu bisfosfonati au fost ineficiente
 o 1.2. BOLI GASTROINTESTINALE: mentinerea unui status ponderal normal; la pcientii cu boala
celiaca – consiliere nutritionala pentru cresterea aderentei la o dieta gluten-free; enzime
pancreatice in cazul malabsorbtiei sec deficitului; B. Crohn: ajustarea imunosupresoarelor si a
dozelor de GC. Exista doua studii care arata ca antiinflamatoare ca infliximab cresc DMO la
pacientii cu boala crohn si poliartrita reumatoida.

2. TRATAMENT SPECIFIC OSTEOPOROTIC

 Vitamina D si calciu: 800-1200 mg/zi calciu din dieta sau suplimentat, >800 UI vit D/zi , in
special pentru ca eficacitatea tratamentului anti-osteoporotic a ost demonstrata in prezenta
unor valori normale ale vitD si CA. Necesaru de suplimentare creste in cazul pacientilor care
sunt pe tratament cu anti-epileptice de tipul fenitoina, fenobarbital, primidone,
carbamazepina, care cresc metabolismul hepatic al vitD.

Absorbtia intestinala a calciului si vit D poate fi sever alterata in b. Crohn, dupa

gastrectomie/chirurgie bariatrica si dupa consumul cronic de IPP: vitD ar trebui administrata
parenteral 100 000-200 000 UI la fiecare 3 luni; o alternativa ar fi administrarea a 50000-100 000 UI o
data/ de doua ori pe sapt.

Un mic studiu randomizat in care au fost comparate alfacalcidiolul si etidronatul la pacientii

transplantati cardiac a indicat faptul ca alfacalcidiolul a fost superior etidronat in prezervarea DMO si
a scaderii riscului de fractura. Un alt studiu, comparand alfacalcidiol cu alendronat la pacientii cu
osteoporoza secundara afectiunilor gastrointestinale, a indicat faptul ca alendronat, dar nu si
alfacalcidiol, a redus riscul de fracturi vertebrale si a crescut DMO. O alta meta-analiza a aratat faptul
ca atat alfacalcidiol, cat si calcitriol, a crescut DMO si a scazut riscul de fractura in special in
osteoporoza non-glucocorticoida. Aceste date sugereaza faptul ca metabolitii activi ai vitD au un rol
important n osteoporoza secundara.

 Bisfosfonati: in special alendronat (70 mg/sapt) si risedronat 35 mg/sapt sunt utilizate in

osteoporoza secundara. In cazul osteoporozei sec. GI, a intolerantei sau contraindicatiilor la
tratamentul oral cu bisfosfonati, se recomanda tratamentul iv cu ibandronat sau acid
zoledronic. Este important de notat faptul ca efectul anti-fractura al bisfosfonatilor este
limitat in Osec, cu exceptia OGI femei si barbati, hipogonadism masculin, barbati dupa
transplant cardiac.

In cazul insuficientei renale, cu MRD eGFR<45 ml/min, la femeile postmenopauza cu osteoporoza,

studiile au aratat eficienta alendronat in scaderea riscului de fractura, pe cand la pacientii cu
osteopenie si in program de hemodializa, acidul ibandronic s-a dovedit superior in cresterea DMO,
fara efecte asupra riscului de fractura.

Osteoporoza indusa de GC: alendronat oral 10 mg/zi si risedronat 5 mg/zi au crescut DMO si au redus
riscul de fractura vertebrala la OGI. Intr-un studiu pe 12 luni, acidul zoledronic a fost superior
risedronat in prevenirea pierderii osoase la OGI, cu cresterea DMO cu 4.1% pe acid zoledronic, fata
de 2.7% pe risedronat – fara evidenta asupra riscului de fractura.

Osteoporoza la barbati: in hipogonadism sau eugonadism,alendronat 10 mg/zi a crescut DMO

vertebrala si femurala, reducat si riscul de fractura cu 80% in decursul a2 ani. Risedronat 5mg/zi a
crescut DMO vertebrala si femurala si a scazut riscul de fractura cu 60 % in decursul a 1an.Acid
zoledronic 5mg/an la pacienti varstnici care au suferit fractura de sold a crescut DMO femurala si a
scazut riscul de fracturi non/oateoporotice cu 35%, scazand mortalitatea cu 28% in decurs a 3 ani.

Deprivare androgenica in cancer prostatic: alendronat oral 70mg/sapt si pamidronat 90mg/3luni s-au
dovedit eficiente in prevenirea pierderii osoase, cresterea DMO vertebrale si femurale, si scaderea
turn-over-ului osos. Acidul zoledrnic 5mg/an previne pierderea osoasa in cazul pacientilor cu cancer
prostatic nemetastazat.

Inhibitori de aromataza in cancerul mamar: risedronat oral 35 mg/zi si ibandronat 150mg/luna reduc
pierderea osoasa; terapia semi-anuala cu 4 mg acid zoledronic pentru 3 ani (trialurile Z-si ZO-FAST)
previne pierderea osoasa la pacientele cu inhibitori de aromataza pentru cancer de san mai mult
decat bisfosfonatii orali.

Diverse: Alendronat oral 70 mg/sapt sau 10 mg/zi s-a dovedit eficient in cresterea DMO la pacientii
cu hiperparatiroidism primar, femei cu DZ tip II, si in osteoporoza din sarcina sau din perioada
lactatiei. Terapia semi-anuala cu acid zoledronic s-a dovedit eficienta la pacientii cu gamapatie
monoclonala de semnificatie necunoscuta. Acid zoledronic 4 mg x 5/an s-a dovedit eficient in
prevenirea pierderii osoase la pacientii cu transplant hepatic. Neridronat iv a crescut DMO vertebrala
si femurala la copiii cu osteogenesis imperfecta (alendronat si pamidronat pot fi substituitori daca
neridronat nu e disponibil).

 Teriparatid – formarea de tesut osos este sever alterata in OGI si in osteoporoza la barbati,
fapt pentru care acestea reprezinta si principalele recomandari.

Osteoporoza indusa de GC: intr-un studiu controlat desfasurat pe parcursul a 18 luni, in care au fost
comparate teriparatid 20 mcg/zi sc si alendronat 10 mg/zi oral administrate la pacientii cu Ogi,
teriparatid a crescut DMO vertebrala cu 7,2%, comparativ cu 3.4% in cazul alendronat, crestere care
a avut loc in primele 6 luni de la initierea trataentului.

 Denosumab: a crescut DMO vertebrala la barbaii cu cancer prostatic si deprivare andogenica,

si a crescut DMO femurala la femeile in tratament cu inhibitori de aromataza in cancerul
mamar.

OSTEOPOROZA INDUSA DE GC