Bone-Loss Management Tool Devised

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MONTREAL—Researchers have developed a treatment algorithm that may help improve physicians' ability to manage bone loss following kidney and kidney/pancreas (KP) transplantation.

The algorithm directs the use of bisphosphonate therapy to patients with the highest risk of fracture.

“Most nephrologists don't do bone medicine after transplantation, so there is a tendency to either do nothing or to use bisphosphonates in a nontargeted fashion,” said investigator Grahame J. Elder, MD, PhD, of the Centre for Transplant and Renal Research, Westmead Millennium Institute, Sydney, Australia. “What we are hoping to do is to give nephrologists a more nuanced perspective through a relatively simple algorithm.” He presented study findings related to the use of the algorithm at the American Society of Bone and Mineral Research annual meeting here.

The algorithm incorporates bone mineral density (BMD) testing results, the presence or absence of vertebral fractures, bone turnover assessed by biochemical markers, and general risks for fracture. These clinical data, which usually are assessed before starting bisphosphonates in the general population, are often overlooked in transplant recipients.

Despite a trend toward reduced glucocorticoid exposure in current immunosuppressive regimens, BMD levels often decline after kidney and KP transplantation, Dr. Elder observed. Post-transplant fracture rates remain high in these patient populations, he added.

A meta-analysis has shown that bisphosphonate therapy and vitamin D supplementation may reduce bone loss at the spine and hip, Dr. Elder pointed out. Both therapies, however, have a potential for adverse effects, and bisphosphonates have been associated with adynamic bone disease. Consequently, the use of bisphosphonates is of particular concern if patients have low bone turnover prior to transplantation or have glucocorticoid-induced suppression of bone formation after their transplant.

“This is a big issue,” Dr. Elder told Renal & Urology News. “These patients are at high risk for fracture, and around 20% suffer a fracture within three years of transplantation.  However, the etiology is complex. These people fit into an osteoporosis-prone group, but they have additional issues of abnormal mineralization, microarchitectural change, and, in many cases, persistent high or low bone turnover, which means that bisphosphonates may not always be the answer.”

He and his colleagues conducted a prospective study to look at the consequences of allocating patients to bisphosphonate therapy or calcitriol therapy using the treatment algorithm they developed.  The study included 155 transplant patients (92 kidney transplant recipients and 63 KP transplant recipients), all of whom were followed for 12 months. Kidney recipients were older than KP recipients (mean age 48 vs. 38 years) and had been on dialysis longer (mean 37 vs. 17 months).

The researchers assessed bone turnover markers, levels of intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D, BMD by dual-energy x-ray absorptiometry, and lateral spine x-rays two to four weeks after transplantation for all patients. Based on these results plus an assessment of other risk factors, patients were allocated according to the algorithm to treatment with bisphosphonate therapy (56%) or calcitriol (44%).  Patients with 25-hydroxyvitamin D levels less than 60 nmol/L (24 ng/mL) also received cholecalciferol.

Dr. Elder said more patients put on bisphosphonate therapy were on hemodialysis compared with peritoneal dialysis and were of longer dialysis vintage. In addition, patients receiving bisphosphonate therapy had lower baseline BMD at the lumbar spine and femoral neck.

At 12 months, BMD increased in the bisphosphonate-treated patients at the lumbar spine and femoral neck but did not change significantly at any site in patients not treated with bisphosphonates, who in general had higher baseline BMD levels.

No significant adverse events were observed in any of the subjects, and bone turnover markers normalized in both treatment groups at 12 months. Targeted treatment using this algorithm reduced bisphosphonate exposure and potential drug-related risks—particularly low bone turnover or adynamic bone disease—while maintaining or improving BMD at all sites, the researchers concluded.

“Patients need to be treated as individuals with individual risks that should be assessed and should influence treatment,” Dr. Elder asserted. “That can be difficult because these patients may be followed by clinicians without a lot of experience in investigation or management of osteoporosis. So we are hoping this algorithm may help guide them away from thinking that one size fits all.”
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