Bariatric surgery rates continue to climb in the setting of increasing obesity throughout the world. While effective at promoting weight loss, a growing body of literature has clearly demonstrated that bone loss and increased fracture risk occurs following bariatric surgery. However, major important questions remain regarding the impact of specific types of bariatric surgery on bone metabolism. Notably, most previous studies were not performed in a randomized manner with respect to the type of weight loss surgery. As such, indication bias exists with respect to current knowledge regarding how specific weight loss surgeries impact bone. Here, a randomized, triple-blind single center study in Norway assessed skeletal endpoints in patients with severe obesity and type 2 diabetes who were randomized to receive either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy weight loss surgery. The primary focus of this study, reported elsewhere, was to assess rates of diabetes remission. Areal bone mineral density in the hip and spine decreased significantly more one year after RYGB than after sleeve gastrectomy. The authors investigated serum bone turnover markers over time in these subjects. Both forms of bariatric surgery led to increases in bone formation and resorption markers, with higher levels of both markers seen after RYGB than sleeve gastrectomy. Importantly, these effects were independently associated with surgical procedure and not resultant weight change. Findings here strongly support the emerging notion that RYGB in particular is linked to high bone turnover and bone loss. While many hypotheses exist as to the underlying mechanism linking RYBG and bone loss, this remains an active and open area of investigation.
Denosumab, a neutralizing antibody against RANKL, is a potent antiresorptive agent that increases bone density and reduces fracture risk. In addition to its major role in osteoclast development, the paracrine-acting cytokine RANKL plays an important role in development and maintenance of the adaptive immune system. As such, a concern has been raised that denosumab treatment may increase risk of malignancies kept at bay by lymphoid surveillance. In this systematic review and meta-analysis of randomized controlled trials , the authors assessed risk of malignancy of denosumab versus comparator in 25 prospective randomized controlled trials. In these trials, >21,000 patients were analyzed who were treated for osteoporosis with either denosumab or control. The risk of malignancy was similar between osteoporosis denosumab dosing (60 mg every 6 months) and control. Drug exposure in these studies was up to 48 months. As such, additional post-marketing surveillance safety data are needed to address longer-term risks of malignancy. Nonetheless, these data are largely reassuring and provide additional evidence of the safety of denosumab therapy for osteoporosis.