Treatment of Osteoporosis
Bisphosphonates (alendronate, risedronate, or zoledronic acid) are the first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men, with strong evidence for reducing hip, vertebral, and nonvertebral fractures. 1, 2
First-Line Treatment: Bisphosphonates
For postmenopausal women and men with osteoporosis, oral bisphosphonates or intravenous zoledronic acid should be prescribed as initial therapy (strong recommendation, high-certainty evidence). 1, 2
Specific Bisphosphonate Regimens:
- Alendronate: 70 mg once weekly or 10 mg daily 1, 2, 3
- Risedronate: 35 mg once weekly, 5 mg daily, 75 mg on two consecutive days per month, or 150 mg monthly 1, 2
- Zoledronic acid: 5 mg IV annually 1, 2
Generic formulations should be prescribed whenever possible due to significantly lower cost with equivalent efficacy. 1, 2
Treatment Duration:
Treat for 5 years initially, then reassess fracture risk to determine whether to continue or take a drug holiday (strong recommendation, moderate-certainty evidence). 1, 2 Extending bisphosphonate therapy beyond 5 years reduces vertebral fractures but not other fractures, while increasing risk for long-term harms including atypical femoral fractures and osteonecrosis of the jaw. 1
Efficacy Evidence:
Bisphosphonates reduce vertebral fractures by approximately 47-56%, hip fractures significantly, and nonvertebral fractures in postmenopausal women with established osteoporosis. 1, 4, 5 Effects appear early (within 6-12 months) and are sustained throughout treatment. 6
Second-Line Treatment: Denosumab
Denosumab 60 mg subcutaneously every 6 months is recommended as second-line therapy for patients with contraindications to bisphosphonates or who experience adverse effects from bisphosphonates (conditional recommendation, moderate-certainty evidence for women, low-certainty evidence for men). 1, 2
Critical Warning:
Denosumab discontinuation causes rebound bone loss and multiple vertebral fractures—patients MUST transition to bisphosphonate therapy after stopping denosumab (high-certainty evidence). 1, 2, 7 This is a mandatory sequential therapy requirement, not optional. 1, 8
Very High-Risk Patients: Anabolic Agents First
For patients at very high risk for fracture, anabolic agents (romosozumab or teriparatide) should be initiated BEFORE bisphosphonates, followed by mandatory transition to bisphosphonates or denosumab. 1, 8, 2
Defining Very High Risk:
Very high risk includes patients with: 8, 2
- Age >74 years
- Recent fracture within 12 months
- Multiple prior osteoporotic fractures
- T-score ≤-3.0
- Fractures despite ongoing bisphosphonate therapy
- High FRAX scores (≥20% for major osteoporotic fracture or ≥3% for hip fracture)
Anabolic Agent Options:
- Teriparatide: 20 mcg subcutaneously daily for up to 24 months; reduces vertebral fractures by 69 per 1000 patients and any clinical fractures by 27 per 1000 patients (high-certainty evidence) 1, 2, 9
- Romosozumab: Conditionally recommended for very high-risk postmenopausal women, limited to 12 monthly doses due to waning anabolic effect 1, 8, 2
After completing anabolic therapy, patients MUST transition to bisphosphonate or denosumab to maintain bone density gains and prevent rapid bone loss (high-certainty evidence). 1, 8, 2 Failure to do so results in serious risk for rebound and multiple vertebral fractures. 1
Agents NOT Recommended
Do NOT use estrogen therapy, estrogen plus progestogen, or raloxifene for osteoporosis treatment (strong recommendation against, moderate-quality evidence). 1, 2 These agents carry unfavorable risk-benefit profiles including: 1
- Increased cerebrovascular accidents
- Venous thromboembolic events (OR 1.63)
- Pulmonary embolism (OR 1.82 for raloxifene)
- Increased breast cancer risk with estrogen plus progestin
- Cerebrovascular death (OR 1.56 for raloxifene)
Calcitonin should not be used as it has weaker efficacy data compared with other options and should only be considered in women with less serious osteoporosis who cannot tolerate any other treatment. 1
Essential Adjunctive Measures for ALL Patients
All patients require the following regardless of pharmacologic treatment: 1, 8, 2
- Calcium: 1000-1200 mg daily (1300 mg for ages 9-18)
- Vitamin D: 800-1000 IU daily (600 IU for ages 9-70,800 IU for ages 71+)
- Weight-bearing and muscle resistance exercises
- Balance exercises and fall prevention counseling
- Smoking cessation
- Alcohol reduction
A serum vitamin D level of at least 20 ng/mL (50 nmol/L) is recommended for good bone health. 1
Screening and Diagnosis
DEXA scanning should be performed in: 1
- All women aged ≥65 years
- Postmenopausal women <65 years with risk factors (history of fragility fracture, weight <127 lb, medications/diseases causing bone loss, parental history of hip fracture)
Treatment is indicated for: 1
- T-score ≤-2.5
- T-score between -1.0 and -2.5 with 10-year FRAX risk of major osteoporotic fracture ≥20% or hip fracture ≥3%
- Low-trauma fracture, even if DEXA does not indicate osteoporosis
Monitoring
Do NOT perform bone density monitoring during the 5-year pharmacologic treatment period (weak recommendation, low-quality evidence). 1 Reassess fracture risk at 5 years to determine continuation versus drug holiday. 1, 2
Common Pitfalls and Adverse Effects
Bisphosphonates:
- Upper GI symptoms: Take with full glass of water, remain upright for 30 minutes after oral bisphosphonates 1, 3
- Contraindications: Esophageal abnormalities, inability to stand/sit upright for 30 minutes, hypocalcemia 1, 3
- Long-term risks: Atypical subtrochanteric fractures, osteonecrosis of the jaw (risk increases with duration >5 years) 1
Denosumab:
- Serious infections: Skin, abdomen, bladder, ear, endocarditis 7
- Severe jaw bone problems (osteonecrosis): Dental examination required before starting 7
- Rebound fractures: NEVER discontinue without transitioning to bisphosphonate 1, 2, 7