Zoledronic acid ups bone density but doesn't reduce fractures
Zoledronic acid (Zometa®, Zomera®, Reclast®, Aclasta®), like other bisphosphonate drugs, slows bone resorption by binding to bone and inducing apoptosis (killing) osteoclasts, the bone cells that clear old bone to make room for new. A study just published in JAMA Internal Medicine adds to the evidence that this strategy, while improving bone mineral density, may not reduce and may even worsen fractures. The authors investigated efficacy and safety of zoledronic acid for treating osteoporosis in frail elderly women.
"We conducted a 2-year, randomized, placebo-controlled, double-blinded study from December 2007 through March 2012. Included were 181 women 65 or older with osteoporosis, including those with cognitive impairment, immobility, and multimorbidity, who were living in nursing homes and assisted-living facilities."
They found when assessing hip and spine bone mineral density (BMD) at 12 and 24 months and adverse events that the zoledronic acid, while increasing bone density, did not produce better outcomes:
"Mean (SE) BMD changes were greater in the treatment group: 3.2 (0.7) and 3.9 (0.7) percentage-point differences in the total hip at 12 and 24 months, respectively, and 1.8 and 3.6 percentage-point differences at the spine; adjusted analyses were similar. The treatment and placebo groups’ fracture rates were 20% and 16%, respectively (OR, 1.30); mortality rates were 16% and 13% (OR, 1.24)."
In words, there was a slight increase in fracture and mortality in the zoledronic acid group.
Zoledronic acid and other bisphosphanates do not improve bone health
Practitioners should certainly bear in mind that osteoporosis is not a calcium deficiency disorder but a failure to maintain the protein matrix of bone, the 'scaffolding' that gives resilience and to which the minerals attach. Noted in Medscape Medical News:
"Bone formation, as measured by serum intact N-terminal propeptide type I procollagen, decreased in the treatment group at 12 and 24 months by 21.9 and 20.4 μg/L, respectively (P < .01). At 24 months, the mean (standard error) adjusted between-group difference was 16.95 (3.15) μg/L at 24 months (P < .001)."
Clinical note
Fundamentals of bone health include vitamin D, nutrient, assimilation, etc., but case management of osteoporosis risk must include addressing the two factors that impair maintenance of the bone protein matrix: chronic inflammation and an adverse hormonal milieu.The author of an accompanying JAMA editorial states:
"Although osteoporosis status (by BMD) was similar across groups, there were more prevalent vertebral fractures in the treatment group...All of these features suggest that the participants treated with zoledronic acid were at greater risk of fracture than those in the placebo group, based on an assessment of nonskeletal risk factors, features unlikely to be modified by zoledronic acid."