What are the contraindications to bisphosphonates in an older adult patient with osteoporosis and a history of fractures?

Contraindications to Bisphosphonates

Bisphosphonates are contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min), uncorrected hypocalcemia, esophageal abnormalities that delay esophageal emptying (for oral formulations), and inability to stand or sit upright for at least 30 minutes after administration (for oral formulations). 1, 2

Absolute Contraindications

Severe Renal Impairment

• Creatinine clearance <30 mL/min is an absolute contraindication to bisphosphonate therapy due to accumulation risk and potential nephrotoxicity 1
• Serum creatinine must be measured before initiating therapy 1
• Intravenous bisphosphonates carry particularly high renal risk in this population 3

Uncorrected Hypocalcemia and Vitamin D Deficiency

• Hypocalcemia must be corrected before starting bisphosphonates, as these drugs can precipitate severe hypocalcemia 1, 2
• Vitamin D deficiency specifically increases hypocalcemia risk and attenuates bisphosphonate efficacy 1, 2
• Target serum 25(OH)D level ≥32 ng/mL before initiating therapy 1
• The risk is highest with IV formulations (zoledronic acid, ibandronate) due to rapid bone uptake and acute suppression of bone turnover 1

Esophageal Disorders (Oral Bisphosphonates Only)

• Esophageal abnormalities that delay esophageal emptying (stricture, achalasia, severe dysmotility) contraindicate oral bisphosphonates 2
• Active upper gastrointestinal disease including esophagitis, gastritis, or peptic ulcer disease represents a relative contraindication 2
• Patients with these conditions should receive IV bisphosphonates instead 4, 3

Inability to Comply with Administration Requirements (Oral Formulations)

• Patients who cannot stand or sit upright for at least 30 minutes after taking oral bisphosphonates are contraindicated from using these formulations 2
• This includes patients with severe arthritis, neurological conditions, or those who are bedridden 2
• IV bisphosphonates are the preferred alternative in these situations 4, 3

Relative Contraindications and Special Precautions

Pregnancy and Childbearing Potential

• Bisphosphonates are incorporated into bone matrix and released slowly over years, creating theoretical fetal risk 4
• Women of childbearing potential require careful counseling about this long-term skeletal retention 4

Dental Procedures and Osteonecrosis of the Jaw Risk

• While not an absolute contraindication, patients requiring invasive dental procedures have increased risk of osteonecrosis of the jaw (ONJ) 4
• ONJ incidence is 0.01-0.3% overall but increases with longer treatment duration 3
• Risk is higher after longer treatment duration (>5 years) 4
• Complete necessary dental work before initiating bisphosphonates when possible 3

History of Atypical Femoral Fractures

• Prior atypical femoral fracture is a relative contraindication to continuing or restarting bisphosphonates 4
• Risk increases with treatment duration beyond 5 years 4
• Asian women have higher risk for atypical femoral fractures 3

Clinical Algorithm for Screening Before Initiation

Before prescribing any bisphosphonate:

1. Measure serum creatinine and calculate creatinine clearance—if <30 mL/min, bisphosphonates are contraindicated 1
2. Check serum 25(OH)D level—if <32 ng/mL, initiate vitamin D repletion before starting bisphosphonates 1, 2
3. Assess for esophageal disorders or inability to remain upright for 30 minutes—if present, use IV formulations instead of oral 4, 3, 2
4. Correct hypocalcemia if present before initiating therapy 1, 2
5. Evaluate dental health and complete necessary invasive dental procedures before starting therapy 3

Alternative Therapies When Bisphosphonates Are Contraindicated

When bisphosphonates cannot be used, denosumab is the recommended second-line agent for both postmenopausal women (moderate-certainty evidence) and men (low-certainty evidence) 4

• Denosumab is particularly useful for patients with renal impairment (CrCl <30 mL/min) or esophageal disorders 3
• For glucocorticoid-induced osteoporosis when oral bisphosphonates are inappropriate, the preference order is: IV bisphosphonates, then teriparatide, then denosumab, then raloxifene (postmenopausal women only) 4