The annual meeting of the American Society for Bone and Mineral Research was held Sept. 16 to 20 in San Diego, and attracted approximately 5,000 participants from around the world, including basic research scientists and clinical investigators in bone and mineral metabolism as well as physicians and other health care practitioners. The conference focused on the latest advances in bone and mineral research as well as the translation of research into clinical practice.
During a clinical update for health care professionals regarding vitamin D, Bess Dawson-Hughes, M.D., of Tufts University in Boston, discussed the target serum 25-hydroxyvitamin D (25[OH]D) level clinical practitioners should aim for in patients and the general older population.
"Evidence from double blind randomized controlled trials indicates that achieving a target level of 26 nmol/L will reduce non-vertebral fracture risk; however, a level of 30 ng/mL is needed to reduce risk of hip fractures. At the level of 30 ng/mL, the risk of falls can also be expected to be reduced by about 20 percent," Dawson-Hughes said. "The published trials have included elders with and without osteoporosis. Therefore, to lower risk of falls and fractures, a target 25(OH)D level of 30 ng/mL is appropriate for both patients and the general older population."
During another talk in the clinical update for health care professionals regarding vitamin D, Catherine Gordon, M.D., of Children's Hospital in Boston, discussed how children and adolescents with some chronic diseases are at very high risk for the development of vitamin D deficiency and, potentially, for a low bone mass. These children need higher doses of vitamin D supplementation to avoid vitamin D deficiency.
"Recent recommendations were reviewed that have been developed by the Institute of Medicine, The Endocrine Society, and the American Academy of Pediatrics," Gordon said. "While the Institute of Medicine and American Academy of Pediatrics' recommendations were developed as population recommendations for healthy individuals, The Endocrine Society geared its recommendations towards those who possess risk factors for either vitamin D deficiency or poor bone health. However, it should be remembered that guidelines are only considerations and are not meant to replace clinical judgment."
Douglas DiGirolamo, Ph.D., of Johns Hopkins University in Baltimore, and colleagues evaluated the short-term use of ActRII (ACVR2) fusion proteins (once-per-week injection of soluble ACVR2/Fc or ACVR2B/Fc for four weeks) in mice as a first step toward identifying whether the anabolic effects of blocking this pathway on the skeleton were direct or indirect.
"We noted dramatic and rapid increases in trabecular bone with both receptor treatments, as well as increases in bone volume in the skull, which wouldn't be subject to load bearing and increased mechanical force or exposed to as much muscle contact as the femur," DiGirolamo said. "These results suggested a direct effect in bone, which we confirmed using primary osteoblast cultures from mice, demonstrating that soluble activin receptor treatment increased osteoblast differentiation. Using a genetic model, we further confirmed that this pathway functions directly in bone, as deletion of ACVR2B from primary mouse osteoblasts also altered osteoblast function."
The investigators are currently in the process of generating genetic mouse models in which they can disrupt these receptors in osteoblasts to better understand how they might function directly in bone development and maintenance without the confounding effects of having a soluble receptor administered systemically.
In another study, Richard Kremer, M.D., of McGill University in Montreal, and colleagues found that oral bisphosphonates, administered for the treatment and/or prevention of osteoporosis, could prevent the development of bone metastasis in women diagnosed with breast cancer.
"Administration of oral bisphosphonates normally used for the treatment of postmenopausal osteoporosis reduced the risk of developing bone metastasis by about 50 percent. This risk reduction was observed in both women with local disease at diagnosis (no evidence of cancer spread to lymph nodes) and women with regional disease at diagnosis (cancer spread to lymph nodes)," Kremer said. "This reduction in risk was observed in women treated before the diagnosis of breast cancer and continued after the diagnosis as well as in women treated after the diagnosis of breast cancer."
However, according to Kremer, among women treated after the diagnosis of breast cancer, the effect was only observed when women were compliant with treatment and when bisphosphonates were taken for a sufficient amount of time. In addition, when bisphosphonates were taken before the diagnosis of breast cancer and then stopped or taken for a short period only after the diagnosis, no effect was observed and, in some cases, the risk of developing bone metastasis was worse.
"A relationship between timing of treatment initiation, treatment duration, and effect was seen and will require further studies," Kremer said.
Huifeng Yun, M.D., M.Sc., of the University of Alabama in Birmingham, and colleagues compared fracture incidence and mortality among Medicare beneficiaries initiating various osteoporosis medications.
"Intravenous zoledronic acid had comparable effectiveness to other osteoporosis medications in lowering hip fracture risk. Non-significant trends suggested some differential benefit once the first six months of treatment were excluded," Yun said.
Compared to intravenous zoledronic acid users, the data revealed that calcitonin and intravenous ibandronate users had an increased rate of clinical vertebral fractures. In addition, calcitonin and parathyroid hormone users had an increased rate of mortality. The investigators could not exclude channeling and residual confounding as potential explanations. The study is currently ongoing, as more research is needed.
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