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Calcium and vitamin D supplementation do not reduce fracture rates
Hubacher et al. found ibuprofen did not reduce the rate of IUD discontinuation related to pain and bleeding, which suggests the clinician may not achieve the anticipated result from ibuprofen therapy for pain and bleeding related to IUD use. More research is needed to understand and develop treatment strategies for pain and abnormal bleeding related to IUD use.2 ADDITIONAL REFERENCES 1. Hatcher RA, Trussell J, Stewart F, Nelson AL, Gates Jr W, Guest F, et al. Contraceptive technology, 18th ed. New York: Ardent Media; 2005. 2. Roy S, Shaw Jr ST. The role of prostaglandin in IUD associated uterine bleeding— effect of a prostaglandin synthetase inhibitor (ibuprofen). Obstet Gynecol 1981;58:101– 6.
CALCIUM AND VITAMIN D SUPPLEMENTATION DO NOT REDUCE FRACTURE RATES Jackson RD, LaCroix AZ, Grass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669 – 83. Osteoporosis is a debilitating disease that decreases independence and increases morbidity primarily in women. Clinicians currently recommend dietary and/or calcium supplementation in an attempt to reduce the morbidity and mortality of this insidious disease. As part of the Women’s Health Initiative (WHI), investigators attempted to identify the efficacy of calcium and vitamin D supplementation on the incidence of hip fracture. Postmenopausal women participating in the WHI Dietary Modification trial or the hormone therapy trials were invited to participate in the calcium and vitamin D trial. Participating women were between the ages of 50 and 79 at the initial screening, and had no known medical condition that would limit the participant’s involvement to less than 3 years. Exclusion criteria included hypercalcemia, renal calculi, and corticosteroid use. The study allowed personal supplementation of up to 1000 mg per day of calcium and 600 mg of vitamin D. Bisphosphonates and calcitonin therapy were allowed. Participants were randomly assigned to placebo or calcium/vitamin D therapy (prepared by GlaxoSmithKline). Active tablets contained 500 mg of calcium carbonate and 200 mg of vitamin D. Participants were instructed to take 2 tablets per day in divided doses. Adherence was validated by interview during telephone or clinic visits every 6 months. Of the 36,282 participants meeting inclusion criteria and agreeing to participate, 684 withdrew, 296 were lost to follow-up, and 1551 died. At the conclusion of the trial, 16,936 participants remained in the calcium/vitamin D supplementation group, and 16,815 participants remained in the placebo group. The groups were similar in age groups, race/ethnicity, and family history of fracture, previous 524
fractures, and falls. The mean age at study onset was 62 years, and the mean body mass index of all participants was 29 kg/m2. More than half of the women were on hormone replacement therapy, and approximately 1% were on other osteoporosis medication. They were also similar in the metabolic equivalent expenditures of physical activity and personal calcium and vitamin D supplementation. The outcome variable of total fractures was defined as all reported clinical fractures other than those of the ribs, sternum, skull or face, toes, and cervical vertebrae. All included fractures were validated by radiologic, magnetic resonance imaging, or operative reports by trained and blinded physicians. A smaller group of participants in each study group (2,431 in the treatment group and 1,201 in the placebo group) also underwent dual-energy x-ray absorptiometry of the lumbar spine, total hip, and total body. All analyses were performed on a time-to-event basis and intention to treat principle. The total number of events and the annualized fracture percentage rates are presented. Linear regression was used to compare rates of change in bone mineral density between groups after adjustment for clinical center, race, or ethnic group. The researchers identified a statistically significant increase in total hip bone mineral density in the treatment group. Small preservation was seen at all intervals, and at year 9 was 1.06%. Increases in spine and whole body bone mineral density in the treatment groups were not statistically significant. Although there was a small but significant finding in the hip bone mineralization density, there were no significant differences in fractures between the groups. During a mean of 7.0 years, there were 2102 fractures (175 hip fractures) in the treatment group and 2158 fractures (199 hip fractures) in the control group. Overall, the hazard ratios for the treatment as compared to the control group and 95% confidence interval are as follows: hip 0.88 (CI 0.72–1.08); clinical vertebrae 0.90 (CI 0.74 –1.10); lower arm or wrist 1.01 (CI 0.90 –1.02). Improved outcomes in hip fractures were noted when participants not adhering at least 80% of the time to study protocol were excluded at year 3.9. In this subgroup, the rate of hip fractures was 0.10 in the treatment group and 0.14 in the control group; hazard ratio ⫽ 0.71 (CI 0.52– 0.97). Comparing the treatment group to the control group resulted in a 29% reduction in hip fractures in the treatment group. However, fracture rates at other sites were not improved, even when nonadherent participants were excluded. This study’s strengths include the large sample from multiple sites with oversight from the National Heart, Lung, and Blood Institute at the National Institutes of Health, thus reducing the risk of a type II error. The large prospective blinded study includes excellent documentation with comparable treatment and control groups. However, the study’s researchers anticipated a greater Volume 51, No. 6, November/December 2006
number of hip fractures, being able to recruit more women over 70 years of age, a lower body mass index of the women, and fewer women on hormone replacement therapy and personal calcium use. The authors noted that the unanticipated confounders reduced the power to 48%, which raises the possibility of a type I error despite the fact that 36,282 enrolled in the study and 32,781 women completed the study. The study is limited by allowing participants in both the treatment and control group to continue their own calcium and vitamin D supplementation. The study also allowed participants to continue other potentially confounding medications. It is therefore difficult to estimate the true strength of the effects seen in the treatment group. Additional statistical analyses excluding participants on personal calcium, vitamin D, hormone replacement therapy, bisphosphonates, and calcitonin would add clarity to the study outcome(s). Metabolic equivalents (MET) are an important tool to estimate the intensity of physical exercise. This tool is especially valuable in evaluating aerobic health promotion activities, such as brisk walking or swimming. Resistance training has been more often associated with reduction of bone demineralization but may be difficult
Journal of Midwifery & Women’s Health • www.jmwh.org
to compare to aerobic physical exercise intensity. The Centers for Disease Control and Prevention considers weight training to be a moderate level of physical exercise or 3– 6 METs.1 It would have been helpful if the researchers described the use of METs as it related to physical activity in the study. Additional statistical analyses might have investigated the effect of different physical activity on bone density or fractures within subjects of the control and treatment groups. Overall, this study suggests that calcium with vitamin D initiated at age 50 years or older may not adequately protect against hip fractures. The improvement in bone mineralization over no additional calcium and vitamin D may be statistically significant but was not clinically significant in this study. However, because of some of the limitations and confounders, the clinician may not want to change their calcium supplementation recommendation based on this single study. ADDITIONAL REFERENCE 1. Department of Health and Human Services, Centers for Disease Control and Prevention. Physical activity for everyone. The components of physical fitness. Available from: http://www. cdc.gov/nccdphp/dnpa/physical/components/index.htm#Strength [Accessed March 22, 2006].
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CALCIUM AND VITAMIN D SUPPLEMENTATION DO NOT REDUCE FRACTURE RATES Jackson RD, LaCroix AZ, Grass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669 – 83. Osteoporosis is a debilitating disease that decreases independence and increases morbidity primarily in women. Clinicians currently recommend dietary and/or calcium supplementation in an attempt to reduce the morbidity and mortality of this insidious disease. As part of the Women’s Health Initiative (WHI), investigators attempted to identify the efficacy of calcium and vitamin D supplementation on the incidence of hip fracture. Postmenopausal women participating in the WHI Dietary Modification trial or the hormone therapy trials were invited to participate in the calcium and vitamin D trial. Participating women were between the ages of 50 and 79 at the initial screening, and had no known medical condition that would limit the participant’s involvement to less than 3 years. Exclusion criteria included hypercalcemia, renal calculi, and corticosteroid use. The study allowed personal supplementation of up to 1000 mg per day of calcium and 600 mg of vitamin D. Bisphosphonates and calcitonin therapy were allowed. Participants were randomly assigned to placebo or calcium/vitamin D therapy (prepared by GlaxoSmithKline). Active tablets contained 500 mg of calcium carbonate and 200 mg of vitamin D. Participants were instructed to take 2 tablets per day in divided doses. Adherence was validated by interview during telephone or clinic visits every 6 months. Of the 36,282 participants meeting inclusion criteria and agreeing to participate, 684 withdrew, 296 were lost to follow-up, and 1551 died. At the conclusion of the trial, 16,936 participants remained in the calcium/vitamin D supplementation group, and 16,815 participants remained in the placebo group. The groups were similar in age groups, race/ethnicity, and family history of fracture, previous 524
fractures, and falls. The mean age at study onset was 62 years, and the mean body mass index of all participants was 29 kg/m2. More than half of the women were on hormone replacement therapy, and approximately 1% were on other osteoporosis medication. They were also similar in the metabolic equivalent expenditures of physical activity and personal calcium and vitamin D supplementation. The outcome variable of total fractures was defined as all reported clinical fractures other than those of the ribs, sternum, skull or face, toes, and cervical vertebrae. All included fractures were validated by radiologic, magnetic resonance imaging, or operative reports by trained and blinded physicians. A smaller group of participants in each study group (2,431 in the treatment group and 1,201 in the placebo group) also underwent dual-energy x-ray absorptiometry of the lumbar spine, total hip, and total body. All analyses were performed on a time-to-event basis and intention to treat principle. The total number of events and the annualized fracture percentage rates are presented. Linear regression was used to compare rates of change in bone mineral density between groups after adjustment for clinical center, race, or ethnic group. The researchers identified a statistically significant increase in total hip bone mineral density in the treatment group. Small preservation was seen at all intervals, and at year 9 was 1.06%. Increases in spine and whole body bone mineral density in the treatment groups were not statistically significant. Although there was a small but significant finding in the hip bone mineralization density, there were no significant differences in fractures between the groups. During a mean of 7.0 years, there were 2102 fractures (175 hip fractures) in the treatment group and 2158 fractures (199 hip fractures) in the control group. Overall, the hazard ratios for the treatment as compared to the control group and 95% confidence interval are as follows: hip 0.88 (CI 0.72–1.08); clinical vertebrae 0.90 (CI 0.74 –1.10); lower arm or wrist 1.01 (CI 0.90 –1.02). Improved outcomes in hip fractures were noted when participants not adhering at least 80% of the time to study protocol were excluded at year 3.9. In this subgroup, the rate of hip fractures was 0.10 in the treatment group and 0.14 in the control group; hazard ratio ⫽ 0.71 (CI 0.52– 0.97). Comparing the treatment group to the control group resulted in a 29% reduction in hip fractures in the treatment group. However, fracture rates at other sites were not improved, even when nonadherent participants were excluded. This study’s strengths include the large sample from multiple sites with oversight from the National Heart, Lung, and Blood Institute at the National Institutes of Health, thus reducing the risk of a type II error. The large prospective blinded study includes excellent documentation with comparable treatment and control groups. However, the study’s researchers anticipated a greater Volume 51, No. 6, November/December 2006
number of hip fractures, being able to recruit more women over 70 years of age, a lower body mass index of the women, and fewer women on hormone replacement therapy and personal calcium use. The authors noted that the unanticipated confounders reduced the power to 48%, which raises the possibility of a type I error despite the fact that 36,282 enrolled in the study and 32,781 women completed the study. The study is limited by allowing participants in both the treatment and control group to continue their own calcium and vitamin D supplementation. The study also allowed participants to continue other potentially confounding medications. It is therefore difficult to estimate the true strength of the effects seen in the treatment group. Additional statistical analyses excluding participants on personal calcium, vitamin D, hormone replacement therapy, bisphosphonates, and calcitonin would add clarity to the study outcome(s). Metabolic equivalents (MET) are an important tool to estimate the intensity of physical exercise. This tool is especially valuable in evaluating aerobic health promotion activities, such as brisk walking or swimming. Resistance training has been more often associated with reduction of bone demineralization but may be difficult
Journal of Midwifery & Women’s Health • www.jmwh.org
to compare to aerobic physical exercise intensity. The Centers for Disease Control and Prevention considers weight training to be a moderate level of physical exercise or 3– 6 METs.1 It would have been helpful if the researchers described the use of METs as it related to physical activity in the study. Additional statistical analyses might have investigated the effect of different physical activity on bone density or fractures within subjects of the control and treatment groups. Overall, this study suggests that calcium with vitamin D initiated at age 50 years or older may not adequately protect against hip fractures. The improvement in bone mineralization over no additional calcium and vitamin D may be statistically significant but was not clinically significant in this study. However, because of some of the limitations and confounders, the clinician may not want to change their calcium supplementation recommendation based on this single study. ADDITIONAL REFERENCE 1. Department of Health and Human Services, Centers for Disease Control and Prevention. Physical activity for everyone. The components of physical fitness. Available from: http://www. cdc.gov/nccdphp/dnpa/physical/components/index.htm#Strength [Accessed March 22, 2006].
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