Research - Fractures / Bone Health
A Review of Potential Beneficial Effects of Honey on Bone Health
Mohd Amir Kamaruzzaman,1 Kok-Yong Chin,2 and Elvy Suhana Mohd Ramli1
Abstract
Bone remodelling is a complex and tightly regulated process. Disruption of bone remodelling skewing towards resorption will cause osteoporosis and increase the risk of fragility fracture. Honey is a natural product containing various bioactive ingredients with health benefits, especially polyphenols. Therefore, honey may be a novel dietary supplement to prevent osteoporosis. This review aims to summarize the current evidence on the effects of honey on bone health. The evidence reported so far indicates a skeletal-beneficial effect of honey in animal models of osteoporosis. However, the number of studies on humans is limited. Honey can protect the bone via its antioxidant and anti-inflammatory properties, primarily through its polyphenol content that acts upon several signalling pathways, leading to bone anabolic and antiresorptive effects. In conclusion, honey is a potential functional food for bone health, but the dose and the bioactive contents of honey need to be verified prior to its application in humans.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Intake of Novel Red Clover Supplementation for 12 Weeks Improves Bone Status in Healthy Menopausal Women
Anne Cathrine Thorup,1 Max Norman Lambert,1 Henriette Strøm Kahr,2,3 Mette Bjerre,4 and Per Bendix Jeppesen1
Abstract
Objective. To investigate the effect by which daily consumption of a novel red clover (RC) extract influences bone health, inflammatory status, and cardiovascular health in healthy menopausal women. Design. A 12-week randomized, double-blinded, placebo-controlled trial involving 60 menopausal women receiving a daily dose of 150 mL RC extract containing 37.1 mg isoflavones (33.8 mg as aglycones) or placebo. Methods. Bone parameters were changes in bone mineral density (BMD), bone mineral content (BMC), and T-score at the lumbar spine and femoral neck. Bone turnover (CTx) and inflammatory markers were measured in plasma and finally blood pressure (BP) was evaluated. Results. RC extract had positive effect on bone health, and only the women receiving the placebo experienced a decline in BMD (P<0.01) at the lumbar spine. T-score at the lumbar spine only decreased in the placebo group (P<0.01). CTx decreased in the RC group with −9.94 (±4.93)%, although not significant. Conclusion. Daily consumption of RC extract over a 12-week period was found to have a beneficial effect on bone health in menopausal women based on BMD and T-score at the lumbar spine and plasma CTx levels. No changes in BP or inflammation markers were found and no side effects were observed.
Source : Evidence Based Complementary and Alternative Medicine
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Plasma phospholipid fatty acids and fish-oil consumption in relation to osteoporotic fracture risk in older adults: the Age, Gene/Environment Susceptibility Study1,2,3,4,5
- Tamara B Harris,
- Xiaoling Song,
- Ilse Reinders,
- Thomas F Lang,
- Melissa E Garcia,
- Kristin Siggeirsdottir,
- Sigurdur Sigurdsson,
- Vilmundur Gudnason,
- Gudny Eiriksdottir,
- Gunnar Sigurdsson,
- Laufey Steingrimsdottir,
- Thor Aspelund,
- Ingeborg A Brouwer, and
- Rachel A Murphy⇑
Abstract
Background: Polyunsaturated fatty acids (PUFAs) may play a role in fracture, but studies have been largely confined to estimates of dietary intake.
Objective: We aimed to examine associations between fatty acids measured in late life and fish-oil consumption in early life, midlife, and late life with osteoporotic fracture risk.
Design: Osteoporotic fractures were determined from medical records over 5–9 y of follow-up in men and women aged 66–96 y. Data were analyzed from 1438 participants including 898 participants who were randomly selected from the Age, Gene/Environment Susceptibility Study, which is an observational study, and 540 participants with incident fracture. Plasma phospholipid fatty acids were assessed by using gas chromatography. Fish-oil consumption was assessed by using validated questionnaires as never (referent), less than daily, or daily. HRs and 95% CIs adjusted for age, education, height, weight, diabetes, physical activity, and medications were estimated by using Cox regression.
Results: In men, the highest tertile of PUFAs, n–3 (ω-3), and eicosapentaenoic acid were associated with decreased fracture risk [HRs (95% CIs): 0.60 (95% CI: 0.41, 0.89), 0.66 (0.45, 0.95), and 0.59 (0.41, 0.86), respectively]. In women, PUFAs tended to be inversely associated with fracture risk (P-trend = 0.06), but tertiles 2 and 3 were not independently associated with risk. Tertile 2 of n–6 and arachidonic acid was associated with fracture risk in women [HRs (95% CIs): 1.43 (1.10, 1.85) and 1.42 (1.09, 1.85), respectively]. Daily fish-oil consumption in late life was associated with lower fracture risk in men (HR: 0.64; 95% CI: 0.45, 0.91). Daily fish-oil consumption in midlife was associated with lower fracture risk in women (HR: 0.75; 95% CI: 0.58, 0.98).
Conclusions: Greater PUFA concentrations may be associated with lower osteoporotic fracture risk in older adults, particularly in men. Critical time periods for n–3 fatty acid consumption may differ by sex.
Source : American Journal of Clinical Nutrition
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Evaluation of a Topical Herbal Agent for the Promotion of Bone Healing
Wing-Sum Siu,1,2,3 Chun-Hay Ko,1,2 Ka-Wing Lam,4 Elaine Wat,1,2 Wai-Ting Shum,1,2 Clara Bik-San Lau,1,2 Kam-Ming Ko,5 Leung-Kim Hung,3 David Tai-Wai Lau,1,5 and Ping-Chung Leung1,2,3
Abstract
A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing.
.....A herbal paste for topical use (CDNR) was thus created with four herbs, namely, Carthami Flos (C), Dipsaci Radix (D), Notoginseng Rhizoma (N), and Rhei Rhizoma (R).
Source : Evidence Based Complementary and Alternative Medicine
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Milk intake and risk of mortality and fractures in women and men: cohort studies
- Karl Michaëlsson, professor1,
- Alicja Wolk, professor2,
- Sophie Langenskiöld, senior lecturer3,
- Samar Basu, professor3,
- Eva Warensjö Lemming, researcher14,
- Håkan Melhus, professor5,
- Liisa Byberg, associate professor1
Abstract
Objective To examine whether high milk consumption is associated with mortality and fractures in women and men.
Design Cohort studies.
Setting Three counties in central Sweden.
Participants Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.
Main outcome measure Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.
Results During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).
Conclusions High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.
Source : British Medical Journal
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Auricular Point Acupressure to Manage Chronic Low Back Pain in Older Adults: A Randomized Controlled Pilot Study
Chao Hsing Yeh,1 Natalia E. Morone,2 Lung-Chang Chien,3 Yuling Cao,4 Huijuan Lu,4 Juan Shen,5 Leah Margolis,1 Shreya Bhatnagar,1 Samuel Hoffman,1 Zhan Liang,1 Ronald M. Glick,6 and Lorna Kwai-Ping Suen7
1School of Nursing, University of Pittsburgh, 3500 Victoria Street, 440 Victoria Building, Pittsburgh, PA 15261, USA
2Department of Medicine, Division of General Internal Medicine, University of Pittsburgh, School of Medicine, Veterans Administration, Pittsburgh Healthcare System, Geriatric Research, Education and Clinical Center, 230 McKee Place Suite 600, Pittsburgh, PA 15213, USA
3Division of Biostatistics, University of Texas, School of Public Health at San Antonio Regional Campus and Research to Advance Community Health Center, University of Texas Health Science Center at San Antonio Regional Campus, 7411 John Smith Drive, Suite 1050 Room 505, San Antonio, TX 78229, USA
4School of Nursing, Fudan University, 305 Fenglin Road, Shanghai, China
5School of Nursing, Suzhou Health College, No. 28 Kehua Road Northern District of Suzhou International Education Park, Suzhou, China
6Departments of Psychiatry, Physical Medicine and Rehabilitation, School of Medicine, University of Pittsburgh, 3811 O’Hara Street, Pittsburgh, PA 15213, USA
7School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong
Abstract
This prospective, randomized clinical trial (RCT) pilot study was designed to (1) assess the feasibility and tolerability of an easily administered, auricular point acupressure (APA) intervention and (2) provide an initial assessment of effect size as compared to a sham treatment. Thirty-seven subjects were randomized to receive either the real or sham APA treatment. All participants were treated once a week for 4 weeks. Self-report measures were obtained at baseline, weekly during treatment, at end-of-intervention (EOI), and at a 1-month follow-up. A dropout rate of 26% in the real APA group and 50% in the sham group was observed. The reduction in worst pain from baseline to EOI was 41% for the real and 5% for the sham group with a Cohen’s effect size of 1.22 (P<0.01). Disability scores on the Roland Morris Disability Questionnaire (RMDQ) decreased in the real group by 29% and were unchanged in the sham group (+3%) (P<0.01). Given the high dropout rate, results must be interpreted with caution; nevertheless, our results suggest that APA may provide an inexpensive and effective complementary approach for the management of back pain in older adults, and further study is warranted.
Source : Journal Evidence Based Complementary and Alternative Medicine
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Protective Effect of Ligustrazine on Lumbar Intervertebral Disc Degeneration of Rats Induced by Prolonged Upright Posture
Qian-Qian Liang,1,2 Dao-Fang Ding,1,2 Zhi-Jie Xi,1,2 Yan Chen,1,2 Chen-Guang Li,1,2 Shu-Fen Liu,1,2 Sheng Lu,1,2 Yong-Jian Zhao,1,2 Qi Shi,1,2 and Yong-Jun Wang1,2
1Institute of Spine, Shanghai University of Traditional Chinese Medicine, 725 Wan-Ping South Road, Shanghai 200032, China
2Department of Orthopaedics & Traumatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Chin
Abstract
Most chronic low back pain is the result of degeneration of the lumbar intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is able to relieve pain, suppress inflammation, and treat osteoarthritis and it has the protective effect on cartilage and chondrocytes. Therefore, we asked whether ligustrazine could reduce intervertebral disc degeneration. To determine the effect of ligustrazine on disc degeneration, we applied a rat model. The intervertebral disc degeneration of the rats was induced by prolonged upright posture. We found that pretreatment with ligustrazine for 1 month recovered the structural distortion of the degenerative disc; inhibited the expression of type X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II collagen; and decreased IL-1β, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising agent for treating lumbar intervertebral disc degeneration disease.
Source : Evidence Based Complementary and Alternative Medicine
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Selenium in Bone Health: Roles in Antioxidant Protection and Cell Proliferation
Huawei Zeng *, Jay J. Cao and Gerald F. Combs Jr.
Grand Forks Human Nutrition Research Center, Agricultural Research Service,
United States Department of Agriculture, Grand Forks, ND 58202, USA;
Abstract
Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Such findings may relate to roles of Se in antioxidant protection, enhanced immune surveillance and modulation of cell proliferation. Elucidation of the mechanisms by which Se supports these cellular processes can lead to a better understanding of the role of this nutrient in normal bone metabolism. This article reviews the current knowledge concerning the molecular functions of Se relevant to bone health.
Conclusion
Selenium is an essential nutrient that appears to play a role in bone health. That role is likely to involve the functions of selenoproteins. Many, if not all, selenoproteins are antioxidant enzymes that participate in maintaining cell redox balance, which is important in the regulation of inflammation and bone cell proliferation/differentiation. Selenium may play additional cellular roles, particularly at supranutritional doses, i.e., doses greater than those required for maximal selenoprotein expression. These include the induction of cell cycle arrest, apoptosis, immune function, and the prevention of the bone resorption through the inactivation of osteoclasts (Figure 2). These cellular activities of Se at both nutritional and supranutritional doses may partially account for the potential protection against rheumatoid arthritis, osteoarthritis, osteoporosis and ROS produced by osteoclasts during bone remodeling.
Source : Journal Nutrients
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Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies
1,2,3
Karl Michaëlsson,Alicja Wolk, Liisa Byberg, Johan Ärnlöv, Håkan Melhus
1From the Department of Surgical Sciences, Orthopedics, Uppsala University, Uppsala, Sweden (KM and LB); the Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden (AW); the School of Health and Social Studies, Dalarna University, Falun, Sweden (JÄ); the Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden (JÄ); and the Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden (HM).
Abstract Background: A reduction in the formation of free radicals and oxidative stress might reduce the rate of bone loss and muscle wasting.
Objective: The objective was to determine whether α-tocopherol intake or serum concentrations are associated with fracture risk in older women and men.
Design: Two cohort studies, the Swedish Mammography Cohort (SMC; n = 61,433 women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1138 men), were used.
Results: During 19 y of follow-up, 14,738 women in the SMC experienced a first fracture at any site (3871 hip fractures). A higher hip fracture rate was observed with lower intakes of α-tocopherol. Compared with the highest quintile of intake, the lowest quintile had a multivariable-adjusted HR of 1.86 (95% CI: 1.67, 2.06). The HR of any fracture was 1.20 (95% CI: 1.14, 1.28). α-Tocopherol–containing supplement use was associated with a reduced rate of hip fracture (HR: 0.78; 95% CI: 0.65, 0.93) and any fracture (HR: 0.86; 95% CI: 0.78, 0.94). Compared with the highest quintile of α-tocopherol intake in ULSAM (follow-up: 12 y), lower intakes (quintiles 1–4) were associated with a higher rate of hip fracture (HR: 3.33; 95% CI: 1.43, 7.76) and any fracture (HR: 1.84; 95% CI: 1.18, 2.88). The HR for hip fracture in men for each 1-SD decrease in serum α-tocopherol was 1.58 (95% CI: 1.13, 2.22) and for any fracture was 1.23 (95% CI: 1.02, 1.48).
Conclusion: Low intakes and low serum concentrations of α-tocopherol are associated with an increased rate of fracture in elderly women and men.
Source : American Journal of Clinical Nutrition
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Accelerating the healing of bone fracture using homeopathy: a prospective, randomized double-blind controlled study
S Sharma1*, N Sharma2, R Sharma1
From International Research Congress on Integrative Medicine and Health 2012 Portland, Oregon, USA. 15-18 May 2012
Purpose
In clinical practice, homeopathy is widely used in the fracture-repair process, which accelerates the healing of fractures, enhances callus formation and reduces pain. But there is no anatomical or scientific evidence yet to prove that. Therefore, the current study was undertaken to test the efficacy of homoeopathy in bone fracture healing.
Methods
The study was conducted as a double blind randomized controlled study with 67patients with acute non-displaced lateral malleolar fracture. Patients were recruited from the Emergency Orthopaedic department, SMS Hospital, Jaipur, India during May 2007 to May 2009. Patients were randomized to either a homoeopathy treatment (n=34) or a control group (n=33). All the patients received standard orthopaedic care through 12 weeks following injury. The treatment group received homoeopathic medicine on the basis of totality of symptoms and individualisation. Outcome measures include radiological assessments and functional tests for healing.
Assessments were taken on 3, 6, 9 and 12 weeks.
Results
Faster healing was reported in the homeopathy group by week 9 following injury, including significant improvement in fracture line (p < 0.0001), fracture edge (p<0.0001), callous formation (p< 0.05) and fracture union (p< 0.0001) in comparison to placebo. There was also lower use of analgesics and less self-reported pain in the homeopathy group.
Conclusion
The study suggests that homoeopathy could enhance anatomical and functional fracture healing.
Source : BMC Complementary and Alternative Medicine 2012, 12(Suppl 1):O61
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No Bones About It: Eating Dried Plums Helps Prevent Fractures and Osteoporosis, Study Suggests
When it comes to improving bone health in postmenopausal women -- and people of all ages, actually -- a Florida State University researcher has found a simple, proactive solution to help prevent fractures and osteoporosis: eating dried plums.
"Over my career, I have tested numerous fruits, including figs, dates, strawberries and raisins, and none of them come anywhere close to having the effect on bone density that dried plums, or prunes, have," said Bahram H. Arjmandi, Florida State's Margaret A. Sitton Professor and chairman of the Department of Nutrition, Food and Exercise Sciences in the College of Human Sciences. "All fruits and vegetables have a positive effect on nutrition, but in terms of bone health, this particular food is exceptional."
Arjmandi and a group of researchers from Florida State and Oklahoma State University tested two groups of postmenopausal women. Over a 12-month period, the first group, consisting of 55 women, was instructed to consume 100 grams of dried plums (about 10 prunes) each day, while the second -- a comparative control group of 45 women -- was told to consume 100 grams of dried apples. All of the study's participants also received daily doses of calcium (500 milligrams) and vitamin D (400 international units).
The group that consumed dried plums had significantly higher bone mineral density in the ulna (one of two long bones in the forearm) and spine, in comparison with the group that ate dried apples. This, according to Arjmandi, was due in part to the ability of dried plums to suppress the rate of bone resorption, or the breakdown of bone, which tends to exceed the rate of new bone growth as people age.
The group's research, was published in the British Journal of Nutrition. Arjmandi conducted the research with his graduate students Shirin Hooshmand, Sheau C. Chai and Raz L. Saadat of the College of Human Sciences; Dr. Kenneth Brummel-Smith, Florida State's Charlotte Edwards Maguire Professor and chairman of the Department of Geriatrics in the College of Medicine; and Oklahoma State University statistics Professor Mark E. Payton.
In the United States, about 8 million women have osteoporosis because of the sudden cessation of ovarian hormone production at the onset of menopause. What's more, about 2 million men also have osteoporosis.
"In the first five to seven postmenopausal years, women are at risk of losing bone at a rate of 3 to 5 percent per year," Arjmandi said. "However, osteoporosis is not exclusive to women and, indeed, around the age of 65, men start losing bone with the same rapidity as women."
Arjmandi encourages people who are interested in maintaining or improving their bone health to take note of the extraordinarily positive effect that dried plums have on bone density.
"Don't wait until you get a fracture or you are diagnosed with osteoporosis and have to have prescribed medicine," Arjmandi said. "Do something meaningful and practical beforehand. People could start eating two to three dried plums per day and increase gradually to perhaps six to 10 per day. Prunes can be eaten in all forms and can be included in a variety of recipes."
Source : Science Daily
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High Dose Vitamin D Prevents Fractures
High doses of vitamin D prevent fractures in older people – as long as they take the substance regularly, researchers reported.
In a meta-analysis, oral doses of at least 800 IU were associated with reductions in the risk of both hip and nonvertebral fractures, according to Heike Bischoff-Ferrari, MD, DrPH, of University Hospital in Zurich, and colleagues.
The analysis differs from previous studies and other meta-analyses in that it looked at how much vitamin D participants actually took, rather than what dose they were assigned to take, Bischoff-Ferrari and colleagues reported in the July 5 issue of the New England Journal of Medicine.
Fractures are common in older people and one strategy to prevent them might be vitamin D supplements, the researchers noted, but studies of the issue have been inconsistent. To try to clarify the matter, they looked for all controlled studies of oral vitamin D, with or without calcium, among people 65 and older.
They included 12 studies and had participant-level data on 30,011 volunteers.
The primary end points were the risks of hip fracture and any nonvertebral fracture, and the primary analyses compared the actual intake of vitamin D supplementation, in quartiles, to the controls, with actual intake calculated as the assigned dose plus any additional supplemental dose, adjusted for adherence.
The study design is important, because it takes into account the biology of vitamin supplementation, according to Robert Heaney, MD, of the Creighton University Medical Center in Omaha, Neb.
In an accompanying editorial in the journal, Heaney argued that the inconsistent outcomes of earlier work might be the result of an overfocus in meta-analyses on the methods used in individual trials.
"The question of how much vitamin D is enough is likely to remain muddled as long as meta-analyses focus on trial methodology rather than on biology," he argued.
But Heaney noted that the results of the current meta-analysis are in accordance with recommendations of the Endocrine Society. "It would appear to be prudent, and probably helpful as well, to ensure an intake at the upper end of the range" that the researchers found effective.
Bischoff-Ferrari and colleagues found that, in an intention-to-treat analysis, there was a nonsignificant 10% reduction in the risk of hip fracture and a significant (at P=0.03) 7% reduction in the risk of nonvertebral fracture.
On the other hand, when they took into account actual vitamin D intake, they found a 30% reduction in the risk of hip fracture but only for those in the highest quartile of intake – 792 to 2,000 IU a day.
The relative risk in that group, compared with controls, was 0.70, with a 95% confidence interval from 0.58 to 0.86, and was significant at P<0.001.
They also found a 14% reduction in the risk of any nonvertebral fracture, but again only in the highest quartile. The relative risk was 0.86, with a 95% confidence interval from 0.66 to 0.96, and was significant at P=0.007.
A sensitivity analysis, not including any outside supplements, had similar results, they reported.
Heaney commented that the benefits of supplements might be affected by baseline levels of vitamin D but noted that such information has not been routinely collected in trials of the substance.
Indeed, baseline levels of hydroxyvitamin D were only available for 4,383 participants, Bischoff-Ferrari and colleagues reported. Despite that, the results among those participants were similar to those in the whole group, they found.
In addition to the absence of baseline hydroxyvitamin D levels, other study limitations included inability to separate calcium and vitamin D intake as those receiving high doses of vitamin D were all taking calcium and lack of trial level data for two of the 14 included trials.
The study was supported by the Swiss National Foundations, the European Commission, and DSM Nutritional Products. Bischoff-Ferrari reported financial links with DSM, Amgen, Novartis, MSD, WILD, Roche, and Nestle.
Heaney reported financial links with the International Dairy Foods Association, the National Dairy Council, the Council for Responsible Nutrition, and the Coca-Cola Co.
Primary source: New England Journal of Medicine
Source reference:
Bischoff-Ferrari HA, et al "A pooled analysis of vitamin D dose requirements for fracture prevention" N Engl J Med 2012; DOI: 10.1056/NEJMoa1109617.
Additional source: New England Journal of Medicine
Source reference:
Heaney RP "Vitamin D -- baseline status and effective dose" N Engl J Med 2012; DOI: 10.1056/NEJMe1206858.
Source : Medpage Today
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