Epidemiology

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Etiology

Primary osteoporosis (most common)

• Type I (postmenopausal osteoporosis): postmenopausal women
  • Estrogen stimulates osteoblasts and inhibits osteoclasts.
  • The decreased estrogen levels following menopause lead to increased bone resorption.
• Type II (senile osteoporosis): gradual loss of bone mass as patients age (especially > 70 years)

Secondary osteoporosis

• Drug induced
  • Most commonly due to systemic long-term therapy with corticosteroids (e.g., in patients with autoimmune disease)

Medication	Possible Mechanism
Anticonvulsants that induce cytochrome P450 (phenobarbital, phenytoin, carbamazepine)	↑ Vitamin D catabolism
Aromatase inhibitors	↓ Estrogen
Medroxyprogesterone	↓ Testosterone & estrogen
GnRH agonists (long term)	↓ Testosterone & estrogen
Proton pump inhibitors	↓ Calcium absorption
Glucocorticoids, Unfractionated heparin	↓ Bone formation

• Endocrine/metabolic: hypercortisolism, hypogonadism, hyperthyroidism, hyperparathyroidism, renal disease

Additional risk factors

• Cigarette smoking
• Immobilization or inadequate physical activity
• Malabsorption (e.g., celiac disease), malnutrition (e.g., diet low in calcium and vitamin D), anorexia

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Pathophysiology

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Clinical features

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Diagnostics

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Treatment

Bisphosphonates

• Alendronate, Risedronate, Ibandronate, Zoledronic acid
• Indications: preferred initial treatment in all patients
• See Paget disease > Bisphosphonates for details

Nonbisphosphonates

Denosumab

• Mechanism of action
  • Monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL)
  • Targets RANKL by mimicking osteoprotegerin → interference in osteoclast maturation → ↓ osteoclast activity

PTH and PTH-related protein analogues

• Teriparatide, Abaloparatide
• Recombinant human parathyroid hormone that increases osteoblastic activity → increased bone growth
  • Pulsatile PTH secretion has an anabolic effect on bone metabolism, stimulating osteoblast proliferation, decreasing osteoblast apoptosis, and inducing increased formation of new bone.  Recombinant PTH analogues (eg, teriparatide) are used to treat severe osteoporosis; these analogues promote bone remodeling by inducing increased resorption of old bone while stimulating a corresponding increase in new bone production, resulting in a net increase in total bone mass (ie, positive bone balance).
  • Also increases gastrointestinal calcium absorption & renal tubular calcium reabsorption

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