The missing piece in post-transplant bone health: tertiary hyperparathyroidism management

Dear Editor,

We read with great interest the comprehensive review by Kurnool et al. ¹ on the treatment of osteoporosis in solid organ transplant recipients. The authors have provided an excellent and thorough overview of therapeutic approaches to post-transplant bone disease, systematically addressing medication options across organ systems.

We would like to provide a more nuanced discussion of tertiary hyperparathyroidism in kidney transplant recipients as it represents a significant contributor to post-transplant bone disease. Given the pharmacologic focus of this excellent review, we hope our contribution provides a complementary perspective that further enriches this comprehensive work.

Persistent and tertiary hyperparathyroidism, which represent a post-transplant continuum of chronic kidney disease–mineral and bone disorder, are significant yet underappreciated contributors to post-transplant bone loss. Studies show that 61.7% of kidney transplant recipients develop persistent hyperparathyroidism, with 21.5% progressing to tertiary hyperparathyroidism within 1 year post-transplant. ² Critically, persistent hyperparathyroidism is independently associated with a 1.6-fold higher risk of death-censored graft loss, with this risk increasing to 4.19-fold in patients with parathyroid hormone levels ⩾300 pg/mL. ³ Beyond graft outcomes, tertiary hyperparathyroidism directly contributes to bone mineral density loss and increased fracture risk, a relationship briefly acknowledged in their review.^1,4

Two principal therapeutic approaches exist for managing post-transplant hyperparathyroidism: calcimimetics and parathyroidectomy. ⁵ Calcimimetic therapy, particularly cinacalcet, has been shown to selectively improve bone mineral density, with studies demonstrating significant increases at the femoral neck and improved T-scores. ⁶ To date, no prospective study has demonstrated that cinacalcet reduces fracture incidence in kidney transplant recipients; available evidence is limited to surrogate endpoints such as bone mineral density. ⁵

When compared directly, parathyroidectomy results in more pronounced and generalized improvements in bone mineral density than calcimimetic therapy. Randomized trials have shown that subtotal parathyroidectomy leads to greater increases in bone mineral density at both the lumbar spine and femoral neck compared to cinacalcet treatment. ⁷ Notably, pre-transplant parathyroidectomy is associated with more substantial gains in bone mineral density than post-transplant surgery, underscoring the importance of timing in therapeutic decision-making. ⁵ However, as with calcimimetics, high-quality data on fracture outcomes after parathyroidectomy in transplant recipients remain limited. ⁸ Nevertheless, some retrospective studies suggest that parathyroidectomy may be associated with a reduced risk of fractures. ⁹

Perhaps most concerning is the substantial undertreatment of post-transplant hyperparathyroidism, with 73% of patients with persistent disease receiving no targeted therapy. This therapeutic gap likely represents a missed opportunity to mitigate skeletal complications in a population already at elevated fracture risk. ²

We commend Kurnool et al. for their excellent review and echo their call for high-quality randomized controlled trials with hard clinical endpoints, including fracture reduction and mortality outcomes, in transplant recipients with hyperparathyroidism-related bone disease.