Source of evidence | Duration of postapproval experience in 2010 | |||
---|---|---|---|---|
RCT | Pharmacovigilance | Case series | ||
Bisphosphonates | Alendronate, 15 years Risedronate, 10 years Ibandronate (oral), 5 years Ibandronate (IV), 4 years Zoledronic acid, 3 years | |||
GI effects | ✓ | ✓ | ||
Musculoskeletal pain | ✓ | |||
Acute-phase reactions | ✓ | ✓ | ||
Atrial fibrillation | ✓ | ✓ | ||
Atypical fracture/delayed fracture healing | ✓ | ✓ | ||
Osteonecrosis of the jaw | ✓ | ✓ | ||
Hypersensitivity reactions | ✓ | ✓ | ||
Renal impairment | ✓ | |||
Denosumab | New agent | |||
Severe infection | ✓ | |||
Osteonecrosis of the jaw | ✓ | ✓ | ||
Cancer | ✓ | |||
SERMs | Raloxifene, 13 years Bazedoxifene, new agent Lasofoxifene, new agent | |||
Hot flushes | ✓ | ✓ | ||
Leg cramps | ✓ | ✓ | ||
Venous thromboembolism | ✓ | ✓ | ||
Stroke | ✓ | |||
Endometrial effects | ✓ | |||
Strontium ranelate | 8 years | |||
Venous thromboembolism | ✓ | |||
Hypersensitivity reactions | ✓ | ✓ | ||
Teriparatide or PTH(1–84) | 8 years | |||
Headache, nausea, dizziness, and limb pain | ✓ | ✓ | ||
Osteosarcoma | ✓ | ✓ |
Adverse Reactions to Bisphosphonates
Gastrointestinal Effects
Musculoskeletal Pain
Acute-Phase Reactions
Atrial Fibrillation
Atypical Subtrochanteric Fracture and Delayed Fracture Healing
Osteonecrosis of the Jaw
Hypersensitivity Reactions
Renal Safety
Adverse Reactions to Denosumab
Infections
Osteonecrosis of the Jaw
Cancer
Adverse Reactions to SERMs
Hot Flushes and Leg Cramps
Venous Thromboembolism
Cardiovascular Events and Stroke
Gynecological Safety
Adverse Reactions to Strontium Ranelate
Venous Thromboembolism
Hypersensitivity Reactions
Adverse Reactions to Teriparatide or PTH(1–84)
Nervous System Disorders
Osteosarcoma
Drug–Drug Interactions in Osteoporosis
Discussion and Conclusion
Prevalence | Strength of association | Consistency of association | Dose–response | Temporality | Biological plausibility | |
---|---|---|---|---|---|---|
Bisphosphonates | ||||||
GI effects (oral formulations) | Common (≥1/100) | ++ | ++ | + | + | + |
Musculoskeletal pain | Common (≥1/100) | + | + | − | + | − |
Acute-phase reactions (IV formulations) | Common (≥1/100) | ++ | ++ | + | + | + |
Atrial fibrillation | Very rare (<1/10,000) | − | − | − | − | − |
Atypical fracture/delayed fracture healing | Very rare (<1/10,000) | ± | − | − | + | + |
Osteonecrosis of the jaw | Very rare (<1/10,000) | − | − | − | − | + |
Hypersensitivity reactions | Very rare (<1/10,000) | + | + | − | + | − |
Renal impairment | Very rare (<1/10,000) | + | + | + | + | + |
Denosumab | ||||||
Severe infection | Common (≥1/100) | + | + | − | + | + |
Osteonecrosis of the jaw | Very rare (<1/10,000) | − | − | − | − | + |
Cancer | Very rare (<1/10,000) | − | − | − | − | − |
SERMs | ||||||
Hot flushes | Very common (>1/10) | ++ | ++ | + | + | + |
Leg cramps | Common (≥1/100) | + | + | + | + | + |
Venous thromboembolism | Uncommon (≥1/1,000 to <1/100) | + | + | + | + | + |
Stroke | Very rare (<1/10,000) | − | − | − | − | − |
Endometrial effects | Very rare (<1/10,000) | + | + | + | + | + |
Strontium ranelate | ||||||
Venous thromboembolism | Very rare (<1/10,000) | + | − | − | − | − |
Hypersensitivity reactions | Very rare (<1/10,000) | + | − | − | + | − |
Teriparatide or PTH(1–84) | ||||||
Headache, nausea, dizziness, and limb pain | Common (≥1/100) | + | + | + | + | + |
Osteosarcoma | Very rare (<1/10,000) | − | − | − | − | ± |