Comparative safety and efficacy of bisphosphonates, denosumab, and parathyroid hormone analogs for osteoporosis following lung transplantation.

Background: Parathyroid hormone (PTH) analogs, denosumab, and bisphosphonates are used to treat osteoporosis but have been associated with infections in the general population. Osteoporosis is a common comorbidity following lung transplantation. However, infections increase the risk of developing chronic lung allograft dysfunction, which reduces survival. Evidence for safe and effective use of PTH analogs, denosumab, or bisphosphonates in lung transplant recipients is lacking.

Methods: This single-center retrospective study evaluated lung transplant patients treated with the PTH analogs teriparatide or abaloparatide, RANKL inhibitor denosumab, or bisphosphonates. The primary outcome of interest was the incidence of infection while on the osteoporosis medication, and a multivariable logistic regression was employed to control for infection confounders. Secondary endpoints were treated allograft rejection episodes, the incidence of new donor-specific antibodies, the incidence of fracture while on medication, and the change in bone mineral density (BMD) from the start to the end of osteoporosis medication use.

Results: Forty-four PTH analog courses and 48 denosumab courses were compared with 92 bisphosphonate courses. Infection incidence was significantly lower in the PTH analog group than the denosumab or bisphosphonate group, but this did not retain significance on multivariable modeling. Treated allograft rejection episodes were higher in those with bisphosphonate use, significantly so when compared to PTH analog patients, but patients treated with bisphosphonates were also started on therapy earlier after their transplant when rejection risk is higher. All agents were effective at increasing BMD of the lumbar spine, none improved BMD of the femoral neck, and only PTH analogs significantly improved hip BMD.

Conclusion: In this retrospective study of lung transplant patients treated for osteoporosis post-transplant, there was no difference in risk of infections in patients treated with PTH analogs, denosumab, or bisphosphonate therapies when examined with multivariable modeling. PTH analogs were the most effective since they significantly improved BMD at both the hip and lumbar spine, whereas denosumab and bisphosphonates only improved lumbar spine BMD. This study supports that PTH analogs and denosumab, despite their association with infection in the general population, may be safely utilized compared to bisphosphonates in the post-lung transplant population for the treatment of osteoporosis, but larger studies are needed to confirm these findings.