Denosumab Ups BMD More Than Bisphosphates After Teriparatide

Becky McCall

May 25, 2017

LISBON, Portugal — Twelve months after stopping teriparatide, sequential osteoporosis treatment with denosumab yields higher additional bone-mineral density (BMD) gain as compared with use of a bisphosphonate, with a more pronounced effect seen at the lumbar spine.

The findings come from a new retrospective analysis presented at the European Congress of Endocrinology (ECE) 2017 by Tomaz Kocjan, MD, an endocrinologist from University Medical Center Ljubljana, Slovenia.

The mean BMD increase at the lumbar spine in patients on denosumab was approximately 0.04g/cm2 compared with no increase in patients on bisphosphonates, reported Dr Kocjan.

Ultimately, treatment for osteoporosis aims to reduce fractures through reducing bone loss.

"There were many more fractures in the bisphosphate group compared with the denosumab group," he said, and although this difference was not statistically significant, "I remind you that these are women with severe osteoporosis," he commented.

In total, 5.7% of patients on denosumab experienced fractures of the rib (one) and other nonvertebral bones (three) compared with 17.1% of patients on bisphosphates (one hip, one spine , one humerus, one radius, one pelvic, one rib, and five other nonvertebral fractures).

Currently in the European Union, teriparatide is the only available osteoanabolic drug for osteoporosis and is reserved for high-risk patients with established disease as second-line treatment. (In the US, a new anabolic agent has just been approved, abaloparatide).

"Use should be limited to 2 years and should be followed with an antireabsorptive drug to prevent bone-mineral-density decline and antifracture efficacy," advised Dr Kocjan.

What's Next After an Anabolic Agent?

Dr Kocjan explained that the ideal antireabsorptive agent after teriparatide is unknown, so the current study was designed to look at this issue.

"We aimed to compare BMD changes after 1 year of therapy with bisphosphonates vs denosumab in women with postmenopausal osteoporosis who had completed treatment with teriparatide."

The retrospective analysis consisted of data from 140 women (average age 74 years, 26 years from menopause) with severe postmenopausal osteoporosis who had been treated with teriparatide for 18 to 24 months between 2006 and 2014 at an outpatient clinic.

They then received treatment with either denosumab (n = 70) or one of a number of bisphosphonates (n = 70) including alendronate, risedronate, ibandronate, or zoledronic acid. All patients also received vitamin D3 1000 IU daily as well as 1200 mg of calcium daily.

The primary end point was change in BMD in the lumbar spine and total hip by DEXA scan, taken at the point of stopping of teriparatide, and after a further 12 months of treatment.

Results were adjusted for confounders including age, BMD, 25-hydroxyvitamin D serum urate, and procollagen type 1 N-terminal propeptide (P1NP) at baseline.

The results indicate a lower BMD increase (especially at the lumbar spine) in patients on bisphosphonates when compared with denosumab and a lower BMD increase at the femoral neck and lumbar spine in patients who had a larger BMD increase on teriparatide (ie, regression to the mean).

The Slovenian clinician noted the limitation of this being a retrospective analysis and said that the small number of patients precluded any definitive safety assessment of the two regimens.

"However, this study does closely resemble real-life clinical practice," he observed.

Asked to comment, Anat Jaffe, MD, an endocrinologist from Hillel Yaffe Medical Center, Hadera, Israel, said she was curious about whether the effects seen were due to differences in mode of action between the two types of agent or whether it could be attributed to variable absorption of bisphosphonates.

"I asked if there was a subgroup that was given zoledronic acid by intravenous administration instead of orally, thereby circumventing the issue of underabsorption, but there were no data on this," she observed.

Drs Kocjan and Jaffe have declared no relevant financial relationships.

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 European Congress of Endocrinology 2017.  May 23, 2017; Lisbon, Portugal. 

 

 

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