Benefits, harms of osteoporosis medications unclear for patients with CKD

Among several gaps in medical knowledge, there was conflicting or insufficient evidence of the effectiveness of bisphosphonates on fractures and safety in transplant recipients and patients with chronic kidney disease.


More research is needed to determine the benefits and harms of osteoporosis medications on bone mineral density (BMD), fracture risk, and safety among patients with chronic kidney disease (CKD), a meta-analysis found.

Researchers at Johns Hopkins University Bloomberg School of Public Health in Baltimore reviewed published studies to uncover the potential benefits and harms of bisphosphonates, teriparatide, raloxifene, and denosumab compared with placebo, usual care, or active control.

The results of a systematic review and meta-analysis were published in the April 11 issue of Annals of Internal Medicine.

There were 13 trials (n=9,850) total, and they included kidney transplant recipients (6 trials), patients who had stage 3 to 5 CKD or were receiving dialysis (3 trials), or postmenopausal women with CKD (4 trials).

Evidence showed that bisphosphonates may slow loss of BMD among transplant recipients, but their effects on fractures and safety in transplant recipients and patients with CKD were not clear, the authors wrote. There was conflicting or insufficient evidence of the effectiveness of bisphosphonates on BMD among patients with CKD who had not received a transplant. The evidence on fracture risk reduction and the safety profile of bisphosphonates among patients with CKD and transplant recipients was limited.

Raloxifene may prevent vertebral fractures but may not improve BMD, the authors wrote. There was low strength of evidence that raloxifene may not be more effective than placebo at increasing BMD but may reduce risk for fractures. However, the evidence was limited to patients with stage 3 to 5 CKD. None of the studies evaluating raloxifene adequately reported on safety.

Effects of teriparatide and denosumab on BMD and fractures were unclear and these medications may increase risk for some adverse safety outcomes, according to the study. Researchers were unable to draw conclusions about the effects of teriparatide and denosumab on BMD and risk for fractures.

For raloxifene, teriparatide, and denosumab, most of the evidence came from subgroup analyses of larger randomized controlled trials. All of these studies were considered to have high risk of bias due to lack of reporting on randomization, allocation concealment, blinding, and attrition, the authors wrote. The results of these trials may have limited applicability to the general population with CKD because they were all conducted among postmenopausal women.

There was limited evidence that denosumab may be associated with increased risk for infections, diarrhea, and hypocalcemia, and teriparatide may be associated with increased risk for hypercalcemia.

“More research is needed to determine the best options for patients across the spectrum of CKD to improve BMD and prevent fractures with minimal risk for adverse outcomes,” the authors wrote. “In particular, we need more data among patients with stage 3 to 5 CKD.”