Who should not receive intravenous (IV) bisphosphonates for osteoporosis?

Contraindications for IV Bisphosphonates in Osteoporosis Treatment

IV bisphosphonates for osteoporosis are contraindicated in patients with severe renal impairment (creatinine clearance <30 mL/min), uncorrected hypocalcemia, vitamin D deficiency, pregnancy, and those requiring dental procedures. 1, 2

Absolute Contraindications

• Severe renal impairment: IV bisphosphonates should not be administered to patients with creatinine clearance less than 30 mL/min due to risk of increased serum creatinine and potential acute renal failure 1, 2
• Uncorrected hypocalcemia or vitamin D deficiency: These conditions must be corrected before initiating IV bisphosphonate therapy as hypocalcemia has been reported in patients with unrecognized vitamin D deficiency 1, 3
• Hypersensitivity: Patients with known hypersensitivity to zoledronic acid or any components of the formulation should not receive IV bisphosphonates 2
• Pregnancy: IV bisphosphonates should be avoided in pregnant women or women planning pregnancy due to potential fetal harm 1, 2

Special Populations Requiring Caution

Women of Childbearing Potential

• IV bisphosphonates should be used only in women of childbearing potential who are at high risk of fracture when oral bisphosphonates and teriparatide are not appropriate 4
• Treatment should be initiated only after a discussion about potential fetal harms in the event of an unplanned pregnancy 4

Organ Transplant Recipients

• Patients with organ transplants on glucocorticoids who have a glomerular filtration rate ≥30 mL/min can be treated according to age-related guidelines 4
• An evaluation by a metabolic bone disease expert is recommended for all patients with a renal transplant before initiating IV bisphosphonate therapy 4
• Denosumab is not recommended for transplant patients due to lack of adequate safety data on infections in adults treated with multiple immunosuppressive agents 4

Children and Adolescents

• In children ages 4-17 years with osteoporotic fractures who are continuing glucocorticoid treatment, IV bisphosphonates should only be used if oral treatment is contraindicated 4
• Oral bisphosphonates are preferred over IV formulations in children due to less potential harm 4

Conditions Requiring Dental Precautions

• Patients requiring invasive dental procedures should delay starting IV bisphosphonate therapy if possible 1
• Poor oral hygiene and recent dental extraction are risk factors for osteonecrosis of the jaw (ONJ) in patients on bisphosphonate therapy 1, 2
• Cancer patients should maintain good oral hygiene and have a dental examination with preventive dentistry prior to IV bisphosphonate treatment 2
• While on treatment, patients should avoid invasive dental procedures if possible 2

Monitoring Requirements

• Before initiating IV bisphosphonate therapy:

  • Assess renal function with creatinine clearance 2, 5
  • Check vitamin D status and correct any deficiency 1, 3
  • Perform dental examination and complete necessary dental procedures 1, 2
  • Optimize calcium intake 1, 2

• During therapy:

  • Monitor serum creatinine prior to each dose 2, 5
  • Regularly check serum calcium, electrolytes, phosphate, and magnesium 2
  • Ensure adequate calcium and vitamin D supplementation 2, 3

Alternative Treatments for Contraindicated Patients

• For patients with renal impairment, oral bisphosphonates may be considered as they appear to have better renal safety 1, 6
• For women of childbearing potential who cannot take oral bisphosphonates, teriparatide is recommended as a second-line therapy 4
• For patients with severe renal impairment, denosumab (except in transplant patients) or raloxifene may be considered as alternative treatments 1, 6

Treatment Failure Considerations

• For adults continuing glucocorticoid treatment who have had a fracture after ≥18 months of oral bisphosphonate treatment or significant bone mineral density loss (≥10%/year), consider switching to another class of osteoporosis medication (teriparatide or denosumab) 4
• IV bisphosphonates may be considered if treatment failure is judged to be due to poor absorption or poor medication adherence to oral bisphosphonates 4