Osteoporosis

NB: Not properly researched. Information from PBL plus

Definition
 Deterioration in bone mass and microarchitecture (skeletal fragility) with increased fragility/T-score <2.5
 Bone mineral density 2.5 standard deviations below normal peak values for young adults
o (T score of -2.5 or less)
 Predisposes bone to fractures
 Can lead to chronic pain, disability, loss of independence

Aetiology
 Primary osteoporosis
o Post-menopausal
 Secondary osteoporosis
o Hyperparathyroidism
o Multiple myeloma
o Malabsorption
o Diabetes mellitus (with/without low BMD)
o Inflammatory bowel disease

Risk factors
 Modifiable
o Smoking RF Mnemonic: SHATTERED
o Alcohol intake  Steroid use >5mg/day prednisolone
o Calcium/vitamin D intake  Hyperthyroidism; hyperparathyroidism,
o Sedentary lifestyle hypercalciuria
o Low BMI  Alcohol and tobacco use
o Sex hormones (Oestrogen)
 Thin (BMI <22)
o Medication (steroid/GCS use)
o Inflammatory bowel disease  Testosterone low (e.g. anti androgen in
o COPD cancer of prostate)
o Cushing’s  Early menopause
o Hyperthyroidism  Renal or liver failure
 Non-modifiable  Erosive/inflammatory bone disease (e.g.
o Previous fractures RA or myeloma)
o Pathological fracture (falling from standing)  Dietary Ca low/malabsorption or
o Genetic predisposition Diabetes mellitus type 1
o Age >60
 Family history
o Post-menopausal women
o Family history
o Gender (Females >> Males)
 Falls risk
o Impaired vision
o Balance

Classification
 Type 1: Post-menopausal
 Type 2: Senile
 Type 3: Secondary
Endocrine GIT Haem Renal Autoimmune Drug-induced
GCS, thyroid, Malabsorption Multiple myeloma CKD GCE-related Heparin, loop
hypogonadism, diuretics, PPI
hyper-PTH, GH def,
acromegaly

 Type 4: Idiopathic osteoporosis

Symptoms
 Asymptomatic until fracture
 History
o Height loss
o Back pain
 On examination
o Kyphosis

Investigations
 Look for causes of secondary osteoporosis (See above)
 Bloods
o Serum vitamin D  look at levels
o Serum calcium, phosphate, alkaline phosphatase, 25(OH) vitamin D – osteomalacia
Disease Serum calcium Serum PO4 Serum PTH Serum ALP
Osteoporosis N N N N/high
Osteomalacia Low Low High High
Hypo-PTH Low High Low
Malignancy High N N ++++

o Thyroid function with PTH levels

o Testosterone/Oestrogen levels
o Creatinine (renal function)
o Serum magnesium (investigate calcium homeostasis)
 FBE
o Anaemic
o Sickle cell disease
o Multiple myeloma (for patients above 60 years)
 LFTs for alcoholism (elevated ALT, AST, GGT)
 Imaging
o Bone density (DEXA scan + quantitative CT) – get T-score at spine and hip (<2.5 = diagnostic)
o Plain XR

Prevention
 Chronic glucocorticosteroid use  bone scan every 6 months
 Lifestyle modifications
o Fall prevention
o Dietary calcium/vitamin D supplementation
 Guidelines
o BMD assessment at or around 65 years of age
o Assess fracture risk using the FRACTURE RISK ASSESSMENT TOOL (FRAX)

Treatment When to treat?

 Non-pharmacological - Postmenopausal PLUS
o Increase BMI - Hx of spine/hip fracture
o Vitamin D and Calcium supplements - FRAX score positive
 Vitamin D only not shown to reduce risk of fractures or
- BMD -2.5 T score or
increase BMD
less
 Calcium intake  1000-1500mg/day
 Vtamin D intake  600-800mgday
 SE: 17% higher risk of kidney stones
o Encourage resistance and weight bearing exercise
 Non-weight bearing exercise = osteoarthritis
 Beneficial to skeletal microarchitecture
o Encourage exercise that promote balance (e.g. yoga,, taichi)
 Improved balance + increase in muscle tone reduces falls risk
 o Stop smoking
 Linked with reduced BMD
o Stop alcohol
 Increased risk of falls
 Medical – anti-osteoporotics
o 1st line
 Bisphosphonates: 1st Alendronate, 2nd line: zoledronic acid (injection), risedronate
 Reduce osteoclast activity/inhibits bone remodelling
 Takes 6-12 months for it to work, usually taken for long-term (5 years)
 Take with a full glass of water on empty stomach, remain sitting up for 30min
 Contraindications: Dysphagia, achalasia, inability to remain upright for 30min, renal
impairment (eGFR <35)
o No need t modify osteoporosis therapy before dental procedures BUT
consideration to stop before major invasive dental surgery
 Common SE: Mild hypocalcaemia, muscle pain, mild GIT irritation
o Zoledronic acid can cause an acute phase reaction (flulike Sx) for 3 days
after first infusion
 Adverse SE: Jaw osteonecrosis (Jaw pain), oesophagitis, atypical fractures, peptic
strictures, severely worsening gastric reflux
o Atypical fracture  1 in 100,000 to 5, in 10,000
o Jaw osteonecrosis  <1 in 100,000 users
o Use of glucocorticoids or immunosuppressive agents (patients with cancer)
may increase the risk
 DRUG HOLIDAY
o Patient can be on bisphosphonates for 5 years
o Consider drug holiday if (1) Asymptomatic, (2) BMD normal/not decreasing
o Holiday for 1 year, then review
o 2nd line
 SORM/SERM – selective oestrogen receptor modulators (raloxifene)
 Inhibits bone resorption, increases spine BMD
 No effect on nonvertebral hip fractures
 Long term use of raloxifine decreases breast cancer risk but increases risk of
thrombotic events (DVT)
 SE: DVT
o 3rd line
 Denosumab
 Binds to RANKL, decreasing the differentiation of osteoclasts
 Can be used in renal impairment!!!
o Others
 Oestrogen
 Inhibits bone resorption and maintains bone formation
 SE: Increased breast cancer AND coronary, cerebrovascular, thrombotic events
 Teriparatide
 Anabolic agent that increases bone formation rather than decreasing resorption
 Benefits of teriparatide are quickly lost when drug is discontinued
 Risk of osteosarcoma, though 1 in 1 million so far
 PTH (teriparatide) – anabonic – increases bone density
 Strontium ranelate
 Calcitronin – decrease osteoclast activity (not in ETG)
 Surgical
o Immobilisation, fixation

Prognosis
 Psychological
o Poor quality of life
 o Dependent living situation
 Overall increased risk of death

Complications
 Fragility fractures
 Can be chronic
 Hip fracture/vertebral compression fracture
 Compromise patient’s quality of life, significant healthcare costs
 FRAX tool: WHO Fracture risk assessment tool
Pathophysiology
 Type 1: Post-menopausal
o Oestrogen deficiency after menopause  accelerated bone loss
o Increased production of TNF by T-cells
o TNF potentiates RANK-L induced osteoclast production
o Reduced absorption of calcium and increased calcium metabolism
o Suppression of OPG release from B-cells, downregulation of OPG reduction from stromal cells
o Result: Reduced calcium, increased osteoclast activity and formation, reduced osteoblast activity and formation  more
bone RESORPTION
 Type 2: Senile
o Accumulation of fat in bone marrow
o Reduced formation of osteoblasts and increased apoptosis of osteoblast
o Increased osteoclast activity due to increased RANKL and decreased apoptosis of osteoclasts
o Same result as above
 Type 3: Secondary
Endocrine GIT Haem Renal Autoimmune Drug-induced
GCS, thyroid, Malabsorption Multiple myeloma CKD GCE-related Heparin, loop
hypogonadism, diuretics, PPI
hyper-PTH, GH def,
acromegaly

o GCS - Most common form

o Cumulative GCS increases risk
o Blocks vitamin D action in calcium absorption
o Decreased in serum calcium, increased serum PTH
o Increased bone resorption
o Decreased GH secretion
o Hypogonadism, bone loss due to inhibitied gonadotropin release
 Type 4: Idiopathic osteoporosis
o Affects young people
o Rare, we do not know why.