Calcium plus vitamin D supplementation and the risk of fractures.

BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P<0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels. CONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

Tobacco-free community coalitions: opportunities for enhancing oral cancer prevention programs.

BACKGROUND: This study identified oral cancer (OC) education and tobacco reduction collaboration within tobacco-free community coalitions (TFCC). METHODS: Data from 4 TFCC were collected via educational intervention surveys and structured focused group Interviews. RESULTS: Of the 52 participants, 96% were aware that tobacco products are risk factors for OC, yet 33% were unaware of the high OC impact locally. About 90% agreed that primary care providers and dentists should provide OC screenings and tobacco cessation. CONCLUSION: There is a need for provider endorsement and public demand for OC screenings. Opportunity exists for partnering and collaborative OC prevention with TFCC.

Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling.

CONTEXT: Daily PTH administration increases bone mineral density (BMD) and reduces fracture risk. However, cost and compliance significantly limit clinical use. OBJECTIVE: Our objective was to determine whether less frequent PTH administration increases lumbar spine BMD. PARTICIPANTS, DESIGN, AND SETTING: Fifty postmenopausal women ages 45-70 yr with femoral neck BMD T-score between -1.0 and -2.0 participated in a double-blind, randomized, placebo-controlled trial at St. Joseph Hospital, Bangor, ME. INTERVENTION: Subjects received sc injections of daily PTH(1-84) (100 mug) or placebo for 1 month, followed by weekly injections (PTH or placebo) for 11 months. OUTCOMES: Change in lumbar spine dual-energy x-ray absorptiometry areal BMD (primary) was assessed. Secondary outcomes included volumetric BMD at spine and hip by quantitative computed tomography, trabecular bone microarchitecture by magnetic resonance imaging of distal radius, and biochemical bone turnover markers. RESULTS: At 12 months, lumbar spine areal BMD increased 2.1% in PTH-treated women compared with placebo (P = 0.03). Vertebral trabecular volumetric BMD increased 3.8% in PTH-treated women compared with placebo group (P = 0.08). PTH-treated women also had higher distal radial trabecular bone volume, number, and thickness compared with placebo-treated women (P < 0.04). After 1 month of daily PTH, N-terminal propeptide of type I collagen (P1NP) was markedly increased compared with placebo (P < 0 .0001), and a difference persisted, although lessened, throughout the study. Bone resorption indices were unchanged in PTH-treated women and were reduced in the placebo group. CONCLUSION: Once-weekly PTH after 1 month of daily treatment increases spine BMD, radial trabecular bone, and bone formation markers in postmenopausal women. These results suggest that less frequent alternatives to daily PTH dosing for 2 yr could be effective. Additional studies are required to define the optimal frequency of PTH administration.

One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis.

BACKGROUND: Since the use of parathyroid hormone as a treatment for osteoporosis is limited to two years or less, the question of whether antiresorptive therapy should follow parathyroid hormone therapy is important. We previously reported results after the first year of this randomized trial comparing the use of full-length parathyroid hormone (1-84) alone, alendronate alone, or both combined. In the continuation of this trial, we asked whether antiresorptive therapy is required to maintain gains in bone mineral density after one year of therapy with parathyroid hormone (1-84). METHODS: In the data reported here, women who had received parathyroid hormone (1-84) monotherapy (100 microg daily) in year 1 were randomly reassigned to one additional year with either placebo (60 subjects) or alendronate (59 subjects). Subjects who had received combination therapy in year 1 received alendronate in year 2; those who had received alendronate monotherapy in year 1 continued with alendronate in year 2. Bone mineral density at the spine and hip was assessed with the use of dual-energy x-ray absorptiometry and quantitative computed tomography (CT). RESULTS: Over two years, alendronate therapy after parathyroid hormone therapy led to significant increases in bone mineral density in comparison with the results for placebo after parathyroid hormone therapy, a difference particularly evident for bone mineral density in trabecular bone at the spine on quantitative CT (an increase of 31 percent in the parathyroid hormone-alendronate group as compared with 14 percent in the parathyroid hormone-placebo group). During year 2, subjects receiving placebo lost substantial bone mineral density. CONCLUSIONS: After one year of parathyroid hormone (1-84), densitometric gains appear to be maintained or increased with alendronate but lost if parathyroid hormone is not followed by an antiresorptive agent. These results have clinical implications for therapeutic choices after the discontinuation of parathyroid hormone.

Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research.

UNLABELLED: ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. INTRODUCTION: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. MATERIALS AND METHODS: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. RESULTS AND CONCLUSIONS: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.

The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis.

BACKGROUND: Parathyroid hormone increases bone strength primarily by stimulating bone formation, whereas antiresorptive drugs reduce bone resorption. We conducted a randomized, double-blind clinical study of parathyroid hormone and alendronate to test the hypothesis that the concurrent administration of the two agents would increase bone density more than the use of either one alone. METHODS: A total of 238 postmenopausal women (who were not using bisphosphonates) with low bone mineral density at the hip or spine (a T score of less than -2.5, or a T score of less than -2.0 with an additional risk factor for osteoporosis) were randomly assigned to daily treatment with parathyroid hormone (1-84) (100 microg; 119 women), alendronate (10 mg; 60 women), or both (59 women) and were followed for 12 months. Bone mineral density at the spine and hip was assessed by dual-energy x-ray absorptiometry and quantitative computed tomography. Markers of bone turnover were measured in fasting blood samples. RESULTS: The bone mineral density at the spine increased in all the treatment groups, and there was no significant difference in the increase between the parathyroid hormone group and the combination-therapy group. The volumetric density of the trabecular bone at the spine increased substantially in all groups, but the increase in the parathyroid hormone group was about twice that found in either of the other groups. Bone formation increased markedly in the parathyroid hormone group but not in the combination-therapy group. Bone resorption decreased in the combination-therapy group and the alendronate group. CONCLUSIONS: There was no evidence of synergy between parathyroid hormone and alendronate. Changes in the volumetric density of trabecular bone, the cortical volume at the hip, and levels of markers of bone turnover suggest that the concurrent use of alendronate may reduce the anabolic effects of parathyroid hormone. Longer-term studies of fractures are needed to determine whether and how antiresorptive drugs can be optimally used in conjunction with parathyroid hormone therapy.

National Institutes of Health Research Plan on Rehabilitation: NIH Medical Rehabilitation Coordinating Committee.

One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public. This article provides an overview of the need for this research plan, an outline of its development, and a listing of six priority areas for research. The NIH is committed to working with all stakeholder communities engaged in rehabilitation research to track progress made on these priorities and to work to advance the science of medical rehabilitation.This article is being published almost simultaneously in the following six journals: American Journal of Occupational Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and Rehabilitation Psychology. Citation information is as follows: NIH Medical Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407.

Tobacco use prevention and cessation in dental and dental hygiene undergraduate education.

Oral health care professionals are aware of their responsibility to advise patients to stop using tobacco. However, they do not feel sufficiently prepared to help their patients to quit, and consequently are not confident in providing these preventive measures. This fact reflects the lack of emphasis on tobacco cessation in both dental and dental hygiene undergraduate education. It may therefore be assumed that improvement of dental and dental hygiene education in tobacco use cessation counselling may result in increased self-confidence and frequency of its provision. The importance of making space in the curriculum for tobacco use prevention and cessation has to be emphasised. Dental schools and dental hygiene programmes have to be reminded of the key role the dental profession has in tobacco control. Next to the public health aspect of tobacco control, such involvement may be both an ethical and a legal responsibility. The implementation of effective tobacco use prevention and cessation in a dental educational setting requires a multidisciplinary approach involving the school's entire teaching personnel and external experts. In general, a knowledge base attained through lecture, Problem-Based Learning (PBL), or E-Learning, and clinical skills attained through clinical instructions and practices is required. It is suggested that curriculum content should include (1) the biological effects of tobacco use, (2) the history of tobacco culture and psychosocial aspects of tobacco use, (3) prevention and treatment of tobacco use and dependence, and (4) development of clinical skills for tobacco use prevention and cessation.

Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study--a large observational study of the determinants of fracture in older men.

Very little information is available to direct the prevention or management of osteoporosis in men. The Osteoporotic Fractures in Men (MrOS) Study is a prospective cohort study designed to examine the extent to which fracture risk is related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, and fall propensity, as well as to determine how fractures affect quality of life in men. The study is also designed to understand how osteoporosis is related to prostate disease. At baseline, participants completed questionnaires regarding medical history, medications, physical activity, diet, alcohol intake, and cigarette smoking. Objective measures of anthropometric, neuromuscular, vision, strength, and cognitive variables were obtained. Skeletal assessments included DEXA, calcaneal ultrasound, and vertebral radiographs. Vertebral and proximal femoral QCT was performed on a subset (65%). Serum, urine, and DNA specimens were collected. After the baseline assessments, a questionnaire is mailed to participants every 4 months to ascertain incident falls, fractures, prostate cancer, and deaths. After an average of 4.5 years, participants are scheduled to return for a second comprehensive visit. Men were eligible if > or =65 years. 5995 men enrolled with a mean (+/-SD) age of 73.7 (+/-5.9) years, 11% of which were minorities. Most rated their health as good/excellent. Few were current smokers, although 59% had smoked previously, and 35% reported no alcohol intake, while 47% consumed at least 2 drinks per week. The mean (range) body mass index was 26.9 kg/m2 (17-56). A non-traumatic fracture after age 50 was reported by 17% of the cohort. The MrOS cohort should provide valuable information concerning the determinants of fracture in men and should help set the stage for the development of effective methods to identify those at risk.

Statin use, clinical fracture, and bone density in postmenopausal women: results from the Women's Health Initiative Observational Study.

BACKGROUND: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to stimulate bone formation in laboratory studies, both in vitro and in vivo. While early epidemiologic studies showed lower risk for hip fracture among statin users than nonusers, subsequent studies have produced mixed results. OBJECTIVE: To examine the association of statin use with incidence of hip, lower arm or wrist, and other clinical fractures and with baseline levels of bone density. DESIGN: Prospective study. SETTING: Women's Health Initiative Observational Study conducted in 40 clinical centers in the United States. PARTICIPANTS: 93 716 postmenopausal women ages 50 to 79 years. MEASUREMENTS: Rates of hip, lower arm or wrist, and other clinical fractures were compared among 7846 statin users and 85 870 nonusers over a median follow-up of 3.9 years. In 6442 women enrolled at three clinical centers, baseline levels of total hip, posterior-anterior spine, and total-body bone density measured by using dual-energy x-ray absorptiometry were compared according to statin use. RESULTS: Age-adjusted rates of hip, lower arm or wrist, and other clinical fractures were similar between statin users and nonusers regardless of duration of statin use. The multivariate-adjusted hazard ratios for current statin use were 1.22 (95% CI, 0.83 to 1.81) for hip fracture, 1.04 (CI, 0.85 to 1.27) for lower arm or wrist fracture, and 1.11 (CI, 1.00 to 1.22) for other clinical fracture. Bone density levels did not statistically differ between statin users and nonusers at any skeletal site after adjustment for age, ethnicity, body mass index, and other factors. CONCLUSION: Statin use did not improve fracture risk or bone density in the Women's Health Initiative Observational Study. The cumulative evidence does not warrant use of statins to prevent or treat osteoporosis.

Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled "Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits." Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying "-omics" technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine.

Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial.

CONTEXT: In the Women's Health Initiative trial of estrogen-plus-progestin therapy, women assigned to active treatment had fewer fractures. OBJECTIVE: To test the hypothesis that the relative risk reduction of estrogen plus progestin on fractures differs according to risk factors for fractures. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial (September 1993-July 2002) in which 16 608 postmenopausal women aged 50 to 79 years with an intact uterus at baseline were recruited at 40 US clinical centers and followed up for an average of 5.6 years. INTERVENTION: Women were randomly assigned to receive conjugated equine estrogen, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOME MEASURES: All confirmed osteoporotic fracture events that occurred from enrollment to discontinuation of the trial (July 7, 2002); bone mineral density (BMD), measured in a subset of women (n = 1024) at baseline and years 1 and 3; and a global index, developed to summarize the balance of risks and benefits to test whether the risk-benefit profile differed across tertiles of fracture risk. RESULTS: Seven hundred thirty-three women (8.6%) in the estrogen-plus-progestin group and 896 women (11.1%) in the placebo group experienced a fracture (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83). The effect did not differ in women stratified by age, body mass index, smoking status, history of falls, personal and family history of fracture, total calcium intake, past use of hormone therapy, BMD, or summary fracture risk score. Total hip BMD increased 3.7% after 3 years of treatment with estrogen plus progestin compared with 0.14% in the placebo group (P<.001). The HR for the global index was similar across tertiles of the fracture risk scale (lowest fracture risk tertile, HR, 1.20; 95% CI, 0.93-1.58; middle tertile, HR, 1.23; 95% CI, 1.04-1.46; highest tertile, HR, 1.03; 95% CI, 0.88-1.24) (P for interaction =.54). CONCLUSIONS: This study demonstrates that estrogen plus progestin increases BMD and reduces the risk of fracture in healthy postmenopausal women. The decreased risk of fracture attributed to estrogen plus progestin appeared to be present in all subgroups of women examined. When considering the effects of hormone therapy on other important disease outcomes in a global model, there was no net benefit, even in women considered to be at high risk of fracture.

Perspectives on the future of bone and joint diseases.

The diseases of bones, joints, and muscles are common, chronic, and very costly to society. While the impact of these diseases falls across the age spectrum, the worldwide growth in the percentage of elderly in the population makes attention to musculoskeletal disorders and conditions particularly critical. An effective prevention strategy, driven by an understanding of the fundamental biology of bone and connective tissue, can only result from an upshift in the efforts of many sectors--public and private, academic, scientific, and patient-based--with new opportunities for partnerships and collaborative efforts flourishing. The Decade of the Bone and Joint can serve as a catalyst in this effort. The National Institutes of Health (NIH) are pleased to join with other national and international organizations to promote new activities and initiatives during the next decade. The NIH Osteoarthritis Initiative is highlighted as an example of a public-private partnership to develop resources and information on the natural history of the disease process that can drive new clinical intervention studies in osteoarthritis. Hopefully, this initiative and others will pave the way for important, scientifically driven prevention strategies during the next decade.

An exploratory study of sodium, potassium, and fluid nutrition status of tube-fed nonambulatory children with severe cerebral palsy.

Children with severe cerebral palsy (CP) often have lower mineral intakes than healthy children. It is unknown if their lower nutrient intakes are adequate to meet their needs. The objective of this study was to examine the sodium, potassium, phosphate, and fluid status of primarily tube-fed nonambulatory children with severe CP. The design consisted of a cross-sectional exploratory study and a clinical trial of sodium supplementation. Nutritional status was determined among primarily tube-fed children (aged 2 to 17 years) with CP based on blood and urine samples, anthropometry, and 3-day food records. Mineral and fluid status was evaluated by a nephrologist blind to nutrient intakes. Twenty children supplied food records, blood samples, and anthropometric measurements, and 16 supplied urine samples. Six (37.5%) of those who provided urine samples were considered possibly dehydrated, as urine osmolality was >600 mmol·kg(-1). Six (60%) of the 10 children with satisfactory fluid status (low urine osmolality) were considered to have a possible dietary sodium deficiency based on a very low urine sodium concentration (<20 mmol·L(-1)). Those considered to have a possible dietary sodium deficiency had a significantly lower sodium intake (48% ± 15% Adequate Intake (AI)) compared with those considered sodium sufficient (73% ± 20% AI) (p = 0.031). One child was considered possibly phosphorus deficient, but none was assessed as likely potassium deficient. The conclusion was that sodium deficiencies were likely prevalent among the children. The findings from this small observational study suggest that sodium intakes for tube-fed children with CP should be maintained near the AI for their age. Hydration status of children receiving hypercaloric formulas should be monitored.