Denosumab, an osteoporosis drug, may slow progression of coronary artery calcification (CAC) and potentially reverse osseous calcification in patients with secondary hyperparathyroidism (SHPT) who have severe cases of high bone turnover, according to new research.
In a study of 21 dialysis patients with low bone mass, treatment with denosumab (60 mg), a human monoclonal antibody, reduced serum calcium and phosphate and resulted in no significant increases in mean CAC volume score (-165 mm3) or Agatston score (-133) over 6 months. In contrast, a control group of 21 age- and sex-matched patients receiving standard therapy experienced significant increases in both mean CAC volume score (188 mm3) and Agatston score (387) from baseline based on serial electrocardiography-gated computed tomography.
Bone mineral density in the femoral neck (15%) and lumbar spine (13%) also significantly increased in denosumab-treated patients, Ming Ting Wu, MD, and colleagues from National Yang-Ming University in Taiwan, reported in Osteoporosis International. No patient received sevelamer, fosrenol, or cinacalcet during the study period.
“The present study demonstrated that denosumab, when administered to patients with SHPT, decreased serum calcium and phosphate and suppressed vascular calcification progression,” Dr Ting’s team wrote. “The extent of CAC could stabilize with denosumab therapy in association with hungry bone syndrome; however, this effect may be limited to patients with higher serum [alkaline phosphatase], compatible with severe high bone turnover.”
Patients were treated with calcitriol (1 μg/day), calcium carbonate (3 g/day), and dialysate of calcium 3.5 mEq/L during the first week of denosumab administration to maintain neutral calcium balance. Severe hypocalcemia developed in 3 of the 21 patients during the first 2 weeks of denosumab. However, no cases of symptomatic hypocalcemia, osteonecrosis of the jaw, infection, or fracture occurred.
According to Dr Ting’s team, nondialysis patients with high-turnover bone disease may be more vulnerable to symptomatic hypocalcemia because they do not have dialysate calcium as a safe buffer. As such, they are unlikely to be good candidates for denosumab. The drug may be a good option for SHPT patients waiting to undergo parathyroidectomy, the authors stated.
Chen CL, Chen NC, Wu FZ, Wu MT. Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study [published online April 3, 2020]. Osteo Intl. doi: 10.1007/s00198-020-05391-3