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.
