Among patients with osteoporosis who have diminished long-term response to bisphosphonate therapy, the addition of eldecalcitol may reduce bone turnover markers and increase bone mineral density, according a study in Osteoporosis and Sarcopenia.
Bisphosphonates may increase bone mineral density, but their efficacy “can diminish over longer treatment periods, and bone mineral density plateaus and even decreases have been encountered regardless of the bisphosphonate usage,” said lead study author Mikio Kamimura, MD, PhD, a researcher at the Kamimura Orthopedic Clinic’s Center of Osteoporosis and Spinal Disorders in Matsumoto, Japan, and colleagues.
Eldecalcitol is an active vitamin D3 derivative approved in Japan for the treatment of osteoporosis. A prior study suggested that bisphosphonate therapy combined with eldecalcitol is more effective than bisphosphonate therapy combined with alfacalcidol, another vitamin D analog, for the treatment of osteoporosis (Tohoku J Exp Med. 2015 Dec;237:339-43.). Investigators had not studied the additive effects of eldecalcitol in patients who are poor responders to long-term bisphosphonate therapy, however.
To examine this question, researchers in Japan conducted a prospective cohort study. Dr. Kamimura and colleagues analyzed data from 42 postmenopausal Japanese women with primary osteoporosis who were poor responders to bisphosphonates – that is, their low lumbar bone mineral density or bilateral total hip bone mineral density did not apparently increase with chronic bisphosphonate treatment over 2 years. The patients had an average age of about 73 years. They received bisphosphonate therapy with alendronate, risedronate, or minodronate. During the study, participants added daily oral eldecalcitol 0.75 mcg/day after breakfast.
The researchers measured markers of bone formation and bone resorption before bisphosphonate therapy, before adding eldecalcitol, and 4 months after starting eldecalcitol. They also assessed measures of bone mineral density.
Serum bone alkaline phosphatase, a bone formation marker, and urinary N-terminal telopeptide of type I collagen, a bone resorption marker, significantly decreased with bisphosphonate therapy. Added eldecalcitol decreased both bone turnover markers further.
Average low lumbar bone mineral density increase rate was 0.2% from 2 to 1 years before eldecalcitol administration, −0.7% during the year before eldecalcitol administration, and 2.9% during 1 year of eldecalcitol therapy. Similarly, mean increase rates of bilateral total hip bone mineral density were 0.2%, −0.7%, and 1.2%, respectively. Mean femoral neck bone mineral density increase rate was 1.1% after eldecalcitol administration, whereas the cohort had no gains with bisphosphonate therapy alone.
In osteoporotic patients exhibiting a poor response to long-term bisphosphonate therapy, the addition of eldecalcitol may represent “a good treatment option,” the authors concluded.
The small sample size, short follow-up period, and lack of evaluation of fracture prevention are limitations of the study, and further studies are needed to confirm these results, the researchers acknowledged.
The authors reported no relevant conflicts of interest.
SOURCE: Kamimura M et al. Osteoporos Sarcopenia. 2019 Jun 28. doi: 10.1016/j.afos.2019.06.001.