Bone resorption by osteoclasts outpaces bone formation by osteoblasts.
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
- Non-Pharmacological (All patients):
- Weight-bearing exercise, smoking cessation, limit alcohol.
- Calcium (1200 mg daily) and Vitamin D3 (800–1000 IU daily) supplementation. c
- Fall prevention strategies.
- Pharmacological Indications:
- DEXA T-score -2.5.
- History of hip or vertebral fragility fracture.
- Osteopenia (T-score -1.0 to -2.5) with FRAX 10-year probability of major osteoporotic fracture 20% or hip fracture 3%.
- First-Line Therapy: Oral Bisphosphonates (Alendronate, Risedronate). c
- Mechanism: Inhibit osteoclasts to decrease bone resorption.
- Administration: Must take on an empty stomach with a full glass of water and remain upright for 30 minutes to prevent pill-induced esophagitis.
- Contraindications: GERD, esophageal stricture, achalasia, CKD (GFR < 30-35 mL/min).
- Key Side Effects: Atypical femur fractures, osteonecrosis of the jaw (ONJ) (rare, linked to long-term use or dental procedures).
- Alternative Therapies:
- IV Bisphosphonates (Zoledronic acid): Used if oral form is contraindicated, not tolerated, or patient has poor compliance.
- SERMs (Raloxifene): Agonist at bone, antagonist at breast/uterus. Used in postmenopausal women with high breast cancer risk. Note: Increases risk of DVT/PE; worsens hot flashes.
- Denosumab (RANKL inhibitor): Subcutaneous injection every 6 months. Safe in patients with CKD.
- Teriparatide (Recombinant PTH): Anabolic agent (stimulates osteoblasts). Reserved for severe osteoporosis (T-score < -3.5 or multiple fractures). Note: Max use 2 years due to potential risk of osteosarcoma.
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