Prevention of Bone Loss in Renal Transplant Recipients

Abstract

Abstract. Renal transplant recipients are at risk of developing bone abnormalities that result in bone loss and bone fractures. These are related to underlying renal osteodystrophy, hypophosphatemia, and immunosuppressive treatment regimen. Although bisphosphonates are useful in ameliorating bone mineral loss after transplantation, it is not known whether their use in renal transplant patients leads to excessive suppression of bone turnover and increased incidence of adynamic bone disease. A randomized, prospective, controlled, clinical trial was conducted using the bisphosphonate pamidronate intravenously in patients with new renal transplants. Treatment subjects (PAM) received pamidronate with vitamin D and calcium at baseline and at months 1, 2, 3, and 6. Control (CON) subjects received vitamin D and calcium only. During months 6 to 12, the subjects were observed without pamidronate treatment. Biochemical parameters of bone turnover were obtained monthly and, bone mineral density (BMD) was obtained at baseline and months 6 and 12. Bone biopsies for mineralized bone histology were obtained at baseline and at 6 mo in a subgroup of subjects who underwent scheduled living donor transplantation. PAM preserved bone mass at 6 and 12 mo as measured by bone densitometry and histomorphometry. CON had decreased vertebral BMD at 6 and 12 mo (4.8 Ϯ 0.08 and 6.1 Ϯ 0.09%, respectively). Biochemical parameters of bone turnover were similar in both groups at 6 and 12 mo. Bone histology revealed low turnover bone disease in 50% of the patients at baseline. At 6 mo, all of PAM had adynamic bone disease, whereas 50% of CON continued to have or developed decreased bone turnover. Pamidronate preserved vertebral BMD during treatment and 6 mo after cessation of treatment. Pamidronate treatment was associated with development of adynamic bone histology. Whether an improved BMD with adynamic bone histology is useful in maintaining long-term bone health in renal transplant recipients requires further study.

Post-Transplantation Osteoporosis

“…In the second year after cardiac transplantation, BMD remained stable, although alendronate and calcitriol were discontinued (44). Similarly, studies demonstrated the efficacy of intravenous ibandronate, zolendronic acid and of pamidronate in the prevention of bone loss after renal, heart, lung, liver and bone marrow transplant recipients, independent of the time following transplantation (23, 40,41,45,46).…”

“…Studies using both intravenous and oral bisphosphonates have shown they are effective to prevent bone loss after transplantation (23, [40][41][42]. Alendronate has been studied in both immediate (43) and long-term (42) transplant recipients.…”

Pathogenesis and Prevention of Bone Loss in Patients Who Have Kidney Disease and Receive Long-Term Immunosuppression

“…Although none of these studies was powered to examine the question of fracture convincingly, the ibandronate-based study by Grotz et al (82) hinted at a reduction in vertebral fractures in the ibandronate-treated group. Coco et al (83) conducted one of the few good studies of bisphosphonate intervention after transplantation in which histologic examination was undertaken. Patients received vitamin D and calcium as background therapy, with randomization to pamidronate or no pamidronate at the beginning of a 12-mo follow-up.…”

“…An important practical issue is whether bisphosphonates satisfy this requirement for safety and efficacy. Available evidence suggests that in transplantation (83) and possibly in CKD 5 as well, the risk of harming bone quality is too high to justify blanket treatment of all patients, at least until such time as fracture reduction is established. In patients with CKD 1 and 2, it is reasonable to extrapolate from the positive results of the studies in "non-CKD" patients (72)(73)(74)(75)(76)91).…”

Bisphosphonates

“…Bisphosphonate treatment blunts that bone loss, reduces fracture risk and is used routinely in many transplant centers (69,70).…”