Osteoporosis
Epidemiology
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
Pathophysiology
Clinical features
Diagnostics
- Primary osteoporosis: Serum calcium, phosphate, and parathyroid hormone (PTH) levels are usually normal
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