Half the Denosumab Dose Still Maintains Bone Density

Researchers published the study covered in this summary on researchsquare.com as a preprint that has not yet been peer reviewed.

Key Takeaways

  • In 114 postmenopausal women with osteoporosis and a moderate risk for fractures but no prior fragility fracture who were on a standard dose of denosumab (Prolia, Xgeva) — 60 mg every 6 months — for a median of 2.5 years, switching to a lower dose (30 mg every 6 months) maintained bone mineral density (BMD) at their hip and radial sites and associated with small improvements in BMD at the lumbar spine, after both 1 year and 2 years, regardless of how long the women had taken denosumab prior to the dose reduction.

  • Study participants had no clinical fractures during 24 months of follow-up following their dose reduction.

  • Older patients had a greater increase in BMD at the lumbar spine.

  • None of the women developed osteonecrosis of the jaw nor had an atypical femoral fracture.

Why This Matters

  • Denosumab reduces the risk of vertebral, nonvertebral, and hip fracture for up to 10 years at the standard dose of 60 mg subcutaneously every 6 months, and study results have documented that stopping this regimen associates with rapid declines in BMD, increases in bone remodeling, and an increased risk of fractures.

  • The reduced denosumab dose of 30 mg every 6 months has not undergone evaluation in clinical trials.

  • Patients who have reached treatment targets with standard denosumab therapy may have concerns about potential rare side effects of long-term full-dose denosumab therapy — osteonecrosis of the jaw or atypical femoral fracture — and may prefer the reduced dose if it still helps maintain their BMD.

  • Low-dose denosumab treatment may be a way to transition to bisphosphonate therapy, but this requires further study.

Study Design

  • The researchers enrolled 114 postmenopausal women aged 50-90 years with osteoporosis and a moderate fracture risk (a 10% to 20% risk of a major osteoporotic fracture over the next 10 years, based on the Canadian Association of Radiologists and Osteoporosis Canada assessment tool and no prior fragility fractures) who had been taking 60 mg denosumab every 6 months for at least a year and opted to switch to the 30 mg dose.

  • Eligible patients also had to have a BMI of 18.5 to 33 kg/m2 and normal lab results for serum calcium (corrected for albumin), parathyroid hormone, 25-hydroxyvitamin D, serum phosphorus, alkaline phosphatase, thyroid-stimulating hormone, hemoglobin, white blood cell count, and platelet count.

  • Enrolled patients underwent BMD measurements at the lumbar spine, femoral neck, total hip, and 1/3 distal radius by dual-energy X-ray absorptiometry (DEXA) at baseline, 12 months, and 24 months. 

Key Results

  • The enrolled women averaged 68 years of age and had been taking the full dose of denosumab for a median of 30 months.

  • After 12 months, compared with baseline, mean BMD at the lumbar spine increased by 2.03% (P < .001), a significant change, and mean BMD was stable at the hip and radial sites.

  • After 24 months, compared with baseline, mean BMD at the lumbar spine increased by 3.44% (P < .001), a significant change, and mean BMD was stable at the other skeletal sites.

  • The clinicians who ran the study identified no clinical fractures among the participants during the 24 months on treatment.

Limitations

  • This was a small, nonrandomized trial without a control group that remained on treatment with the standard denosumab dose of 60 mg every 6 months.

  • Few patients (<20% of the study cohort) had not previously received bisphosphonate treatment so it was not clear how prior bisphosphonate use may have affected changes in BMD after switching to low-dose denosumab.

  • Women in the study did not undergo morphometric vertebral evaluation by spine x-rays so uncertainty remains about the incidence of fractures following the change in denosumab dose.

  • The administered 30-mg dose of denosumab was estimated because denosumab is not marketed in a 30-mg vial.

  • The only measured marker of bone turnover was alkaline phosphatase.

Disclosures

  • The study did not receive commercial funding.

  • Lead author Aliya Khan, MD, received research grants for unrelated research projects from Alexion, Amgen, Ascendis, Chugai, Radius, Takeda, and Ultragenyx. All other authors reported no relevant financial or nonfinancial disclosures.

This is a summary of a preprint research study, “Effect of low dose denosumab on bone mineral density in postmenopausal women with osteoporosis after a transition from 60 mg dose: A prospective observational study” written by researchers primarily at McMaster University, Hamilton, Canada, on Research Square, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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