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Bone-Building Drug denosumab Targets Periphery hip, new imaging study identifies sub-regions of bone change with therapy
 
 
  By Michael Smith, North American Correspondent, MedPage Today
Published: October 17, 2010
 
Bone Structure
Woven cortical bone is better defined at the 1st structural level by what it lacks rather than by what it contains. For instance, woven bone does not ... www.engin.umich.edu/.../bonestructure/bonestructure.htm
 
Hip - Wikipedia, the free encyclopedia
The bones of the hip region are the hip bone (or innominate bone) and the ... Prominent palpable bony structures of the hip bone include the iliac crest, ... en.wikipedia.org/wiki/Hip
 
Action Points
 
* Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
 
* Explain to interested patients that preliminary data from a recent study indicates that the osteoporosis drug denosumab (Prolia) preferentially builds bone in the cortical and subcortical regions.
 
* Note that these improvements in bone are thought to be responsible for a 40% reduction in hip fractures, compared with placebo.
 
TORONTO - The osteoporosis drug denosumab (Prolia) preferentially builds bone in the cortical and subcortical regions, a researcher said here.
 
The finding, from an imaging substudy of the large randomized FREEDOM trial, may give some insight into how the drug reduces the risk of hip fractures, according to Harry Genant, MD, of the University of California San Francisco.
 
The imaging study - a planned analysis - used quantitative computed tomography (QCT) combined with software that allowed the researchers to measure bone mineral density in sub-regions of the hip, Genant reported at the annual meeting of the American Society for Bone and Mineral Research here.
 
The 36-month FREEDOM study found that denosumab -- a fully human monoclonal antibody to RANKL, which is involved in bone breakdown - led to a 40% reduction in hip fractures, compared with placebo. Fractures in other sites were also reduced.
 
Patients in the FREEDOM study received 60 mg denosumab or placebo every six months for three years, and all subjects received daily supplements of calcium and vitamin D.
 
The substudy, aimed at understanding the effects on the hip, originally included 45 women from the denosumab arm and 36 from the placebo arm, all of whom had QCT scans at 12, 24 and 36 months. The 36-month results from 19 participants were excluded because of a scanner malfunction, Genant and colleagues reported.
 
But data from the remaining 62 women showed marked differences between the two arms in the percentage of bone mineral density and content in all regions of the hip, Genant said, with the largest coming in the trabecular bone.
 
For example, the average difference between the two groups at month 36 in trabecular bone mineral density was about 17%, Genant said, compared with about 5% for cortical bone and 8% for subcortical bone.
 
The pattern was similar for percentage change in bone mineral content, Genant said, implying that "you do not have substantial changes in volume during the treatment period."
 
But, importantly, analysis of absolute changes showed that most of the new bone was built in the peripheral regions, he said. Specifically, at month 36:
 
* The average gain in trabecular bone was seven milligrams per cubic centimeter in the denosumab patients, compared with a loss of five in the placebo patients.
* The average gain in cortical bone was 29 milligrams per cubic centimeter in the denosumab patients, compared with a gain of two in the placebo patients.
* The average gain in subcortical bone was 14 milligrams per cubic centimeter in the denosumab patients, compared with a loss of three in the placebo patients.
* Within the cortical bone, denosumab patients gained 30 milligrams per cubic centimeter in the periosteal region and 26 in the endosteal region, compared with gains of two and 0.3 milligrams per cubic centimeter, respectively, among placebo patients.
 
The absolute change, Genant said, "is higher in the cortical and subcortical relative to the trabecular."
 
In other words, he concluded, "much of the added bone is coming in the more peripheral regions of the trabecular and the cortical bone."
 
The findings are "not unexpected," said Nancy Lane, MD, of the University of California Davis, who was not part of the study but who moderated the session at which it was presented.
 
"It's what you see with an anti-resorptive (drug) - a thickening of cortical bone because there's not very much trabecular bone there," she told MedPage Today.
 
The important aspect is that the QCT technology allows researchers to see exactly where new bone is being laid down. "It explains a bit where the bone strength is coming from," she said.
 
The FREEDOM trial was supported by Amgen. Genant reported financial links with Amgen, Merck, GSK, Roche, Servier, BMS, Lilly, and Synarc.
 
Lane had no disclosures.
 
Primary source: ASBMR 2010
 
Source reference:
Genant HK, et al. "Hip QCT Results From the FREEDOM Trial: Evidence for Positive BMD/BMC Changes in Integral,
Trabecular, and Cortical Bone With Denosumab." ASBMR 2010; abstract FR0410
 
 
 
 
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