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Experts discuss indications for vitamin D, bisphosphonate therapy in menopause
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When it comes to bone health in the menopausal population, emerging misconceptions on when to begin or halt calcium, vitamin D and bisphosphonate treatments have resulted in a surge of guidelines and recommendations published throughout the literature. However, experts here agreed that further clarification can be made based on evidence.
Clifford Rosen, MD, director of clinical and translational research at Maine Medical Center in Scarborough, Maine; senior scientist at Maine Medical Center Research Institute; adjunct staff scientist at The Jackson Laboratory and professor of medicine at Tufts University in Boston, told Endocrine Today the big issue is that “everybody wants to associate vitamin D with disease or with a health status. It’s not a biomarker for disease, it just tells you how much sun exposure a person has had, and how much to supplement.”
Clifford Rosen
The mistake providers make, he said, is ordering vitamin D in the first place.
“Once you get a level, you want to treat it because it’s a number and if people define it as low, even if it isn’t low, and you give vitamin D, the number goes up. Why order the vitamin D in the healthy individual? It’s not a predictor of disease. I think that’s where it starts.”
Controversies in data
Rosen briefly discussed a recent letter to the editor published in The New England Journal of Medicine, in which he and Susan T. Mayne, PhD, of Yale School of Public Health, wrote that they were concerned about flaws in the meta-analysis and accompanying editorial by Bischoff-Ferrari and colleagues on vitamin D supplementation.
“The meta-analysis ignores the accepted protocol of using intention-to-treat as the primary analysis of randomized, controlled trials and instead relies on more biased secondary analyses to support the conclusion,” Rosen and Mayne wrote.
“More specifically, taking baseline intake (which tracks with health behaviors) and adding compliance-adjusted analyses (known to introduce bias) to estimate actual exposure and then comparing results to the entire control population introduces confounding — such as striking imbalances in measured confounders (eg, calcium intake) and unmeasured confounders across quartiles of vitamin D intake — that completely undermines the value of randomization.”
Recommendations for use of bisphosphonates
Nelson B. Watts, MD, director of Mercy Health Osteoporosis and Bone Health Services in Cincinnati, followed Rosen’s presentation, citing the wide use of bisphosphonates for the treatment of osteoporosis, and explored the usage in patients with osteonecrosis of the jaw (ONJ) and atypical femur fractures (AFF).
“Bisphosphonates represent the first non-hormonal agents that were approved for osteoporosis. Alendronate was approved in 1995. And since 1995, they have been the leading products for the treatment of osteoporosis in part because three of four agents (ie, alendronate, risedronate and zoledronic acid) have evidence for reducing the risk of hip fracture, which is the most serious consequence of osteoporosis,” Watts said during a presentation.
“Bisphosphonates are unique in that they bind to bone mineral; they concentrate at sites of active bone resorption.”
According to Watts, the short-term side effects of using bisphosphonates include hypocalcemia, esophageal irritation, acute phase response, acute renal damage and musculoskeletal pain. The long-term safety concerns include ONJ and AFF, he added.
Nelson B. Watts
Watts recommends discontinuation of bisphosphonates among patients who did not need treatment in the first place. For lower risk patients, if bone density scan (DXA) is stable or increasing, providers should consider a drug holiday after 3 to 5 years of treatment, he said. Higher-risk patients (ie, those who have fractures, are taking corticosteroid medications or have a very low BMD) could be considered for a drug holiday after about 10 years of treatment.
Watts said that providers can use teriparatide or raloxifene during the drug holiday. However, he recommends against using other potent anti-resorptive agents.
Return from drug holiday
Watts said the drug holiday should end based on several factors. Using empiric reasoning, providers could decide that the holiday should be longer for drugs with the highest skeletal relationship (ie, zoledronic acid), and a shorter duration for drugs with the lowest skeletal similarity (ie, residronate). However, many patients will have been on more than one agent, he said. Other factors to consider include bone turnover markers and BMD.
According to Watts, the risk-to-benefit ratio is favorable for most patients at high risk for developing a fracture, and the length of treatment depends on the fracture risk. Although risks for ONJ and AFF may increase after 5 years, Watts said the likelihood of this is still low.
In order to assess ONJ and AFF, Watts recommends looking in the mouth and correcting ONJ prior to treatment. For AFF, he suggests instructing patients to report thigh or groin pain and conduct further investigation with radiographs or other imaging tools for any patient who states they have a femur fracture.
References:
- Bischoff-Ferrari HA. N Engl J Med. 2012; 367:40-49.
- Rosen C, Mayne ST. N Engl J Med. 2012; doi: 10.1056/NEJMc1209658.
- Rosen C. Plenary Symposium #3: Vitamin D & Calcium: Why Such Confusion?
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Watts N. Plenary Symposium #3: Bisphosphonate Drug Holiday: To Be, or Not to Be?
Disclosure:
- Rosen has no relevant financial disclosures. Watts receives consultancy fees from Amgen, Baxter, Bristol-Myers Squibb, Eli Lilly and Company, Imagepace, Johnson & Johnson, Medpace, Merck, Orexigen Therapeutics Inc., and Pfizer. He has received grant support from Amgen, Merck, NPS Pharmaceuticals; speakers’ fees from Amgen, Eli Lilly and Company, Novartis, Warner Chilcott and holds interest with OsetoDynamics.
For more information:
- Clifford Rosen, MD, can be reached at the Center for Clinical & Translational Research, Maine Medical Center Research Institute, 81 Research Dr., Scarborough ME, 04074; email: rosenc@mmc.org.
Perspective
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Nanette F. Santoro, MD
We’ve been saying calcium and vitamin D are great for patients, with no downside, for years. It’s such a simple self-help tool. However, I suppose they have to modify what we do. I would suggest that other providers make sure patients are getting enough calcium in their diet; which they can do. Typically, I send my patients to the National Osteoporosis Foundation website so they can look it up and to supplement very judiciously.Click Here to Manage Email Alerts