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Denosumab may replace bisphosphonates in improving bone strength in postmenopausal osteoporosis

Stephen Padilla
04 Jul 2019

Denosumab is an effective alternative to bisphosphonate as first-line treatment for postmenopausal osteoporosis, suggests a Singapore study.

“There is currently insufficient data to show that denosumab is not inferior to bisphosphonates in fracture prevention,” according to researchers.

A systematic search was conducted in databases including PubMed and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) that directly compared denosumab and bisphosphonates. Studies assessing the two drugs in postmenopausal women with osteoporosis and had a Jadad score ≥3 were included.

Nine studies met the eligibility criteria and were further categorized into six cohort groups, all of which had denosumab with oral bisphosphonates as the active comparator.

Of the six cohort studies, four reported significant improvements in bone strength (p<0.001) at the distal radius, tibia, total hip, femoral neck, lumbar spine and trochanter at 12 months for patients on denosumab compared to those on bisphosphonates. The denosumab group also showed a consistently lower serum C-telopeptide of crosslinked collage, a bone turnover marker, in all studies. [Singapore J Med 2019;doi:10.11622/smedj.2019028]

No significant differences were found in hypocalcaemia, atypical fractures, fragility fractures, osteonecrosis of the jaw, all infections (including fever or influenza-like symptoms), gastrointestinal side effects or dermatological conditions in all studies, except for one that did not document side effects.

A study by Zebaze and colleagues showed less porosity with denosumab than with alendronate. In addition, denosumab showed better efficacy on cortical vs trabecular bone. Of note, 80 percent of bone is cortical and 70 percent of all appendicular bone loss is cortical. Additionally, 80 percent of fractures in women aged >65 years are nonvertebral. [Bone 2014;59:173-179; Bone 2005:36:22-32]

“Given the aforementioned factors, it stands to reason that denosumab is effective in reducing intracortical bone remodelling in women with postmenopausal osteoporosis,” researchers said.

Medication adherence was also better with denosumab than with bisphosphonates. In a study by Kendler and colleagues, patients reported greater satisfaction when they transitioned to denosumab as compared to switching to monthly oral bisphosphonates. [Menopause 2014;21:25-32]

Another study showed that patients had more positive perceptions of and preferred denosumab to alendronate while on treatment, and this subsequently correlated with better adherence. [J Clin Endocrinol Metab 2015;100:E487-92]

However, denosumab costs nearly eight times more than a yearly supply of generic bisphosphonates (approximately SGD 800/year for two injections). In addition to this, the fear of needles could deter treatment among patients.

“These are important considerations that need to be discussed with the patient to allow her to make an informed choice, and to individualize the treatment for postmenopausal osteoporosis,” researchers said. “Nevertheless, for those with intolerance or contraindications to bisphosphonate, denosumab is an effective alternative.”

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