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Vitamin D supplementation and bone health in menopausal women: a systematic review of randomised controlled trials
Abstract
Serum 25(OH)D (vitamin D) plays an important role in skeletal and muscle function ⁽¹⁾ . Menopausal women are at an increased risk of reduced bone mineral density (BMD) and fracture due to a decline in oestrogen levels ⁽²⁾ . A low circulating 25-hydroxyvitamin D (25(OH)D) level during menopause is a common problem and has been associated with changes in dietary intake and body composition ⁽³⁾ . While vitamin D supplementation has been shown to increase serum 25(OH)D levels, its isolated effects on bone health in menopausal women is largely misunderstood. A systematic review was conducted to identify, appraise, and synthesise available studies to assess the impact of vitamin D supplements and bone health in menopausal women.
Four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to 8 December 2023. Only randomised controlled trials (RCTs) examining the efficacy of vitamin D supplementation in menopausal and/or post-menopausal women were included. Studies published in English and measuring BMD, fracture risk, calcium absorption, or serum 25(OH)D levels were eligible. Animal/lab trials, studies involving pharmaceutical co-treatments or vitamin K and/or calcium supplements were excluded. Two researchers independently extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines ⁽⁴⁾ and assessed possible bias using the Cochrane risk of bias tool v2. A narrative approach was used to synthesise the data.
In total, 243 studies were retrieved through initial database searches. Following the elimination of duplicates and screening stages, six RCTs involving 696 menopausal women met the eligibility criteria. The studies varied in intervention length (range 4 wks-4 yrs) and were conducted across four different countries including: Brazil, Bangladesh, Japan, and the USA. Study samples ranged from 38 to 230 participants. A variety of vitamin D supplements (dosages/frequencies) were used across the included studies. Despite heterogeneity in study methods and vitamin D dosages, significant improvements were observed in BMD, risk of falls, and calcium absorption following vitamin D supplementation. Results also found that vitamin D supplementation may improve postural balance and muscle function, improving mobility for menopausal women.
This systematic review demonstrates that vitamin D supplementation can enhance BMD, calcium absorption, reduce the risk of falls, and improve postural balance in menopausal women. However, the optimal dosage of vitamin D has not been determined. Limitations include methodological heterogeneity and lack of long-term follow-up, highlighting the need for further large-scale RCTs with rigorous methodology. These findings underscore the importance of ongoing research to better understand the role of vitamin D supplementation and bone health in menopausal women.
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Vitamin D is a critical regulator of calcium and bone homeostasis. While vitamin D has multiple effects on bone and calcium metabolism, the regulation of intestinal calcium (Ca) absorption efficiency is a critical function for vitamin D. This is necessary for optimal bone mineralization during growth, the protection of bone in adults, and the prevention of osteoporosis. Intestinal Ca absorption is regulated by 1,25 dihydroxyvitamin D (1,25(OH)2 D), a hormone that activates gene transcription following binding to the intestinal vitamin D receptor (VDR). When dietary Ca intake is low, Ca absorption follows a vitamin-D-regulated, saturable pathway, but when dietary Ca intake is high, Ca absorption is predominately through a paracellular diffusion pathway. Deletion of genes that mediate vitamin D action (i.e., VDR) or production (CYP27B1) eliminates basal Ca absorption and prevents the adaptation of mice to low-Ca diets. Various physiologic or disease states modify vitamin-D-regulated intestinal absorption of Ca (enhanced during late pregnancy, reduced due to menopause and aging).
Among the various aspects of health promotion and lifestyle adaptation to the postmenopausal period, nutritional habits are essential because they concern all women, can be modified, and impact both longevity and quality of life. In this narrative review, we discuss the current evidence on the association between dietary patterns and clinical endpoints in postmenopausal women, such as body composition, bone mass, and risk markers for cardiovascular disease. Current evidence suggests that low-fat, plant-based diets are associated with beneficial effects on body composition, but further studies are needed to confirm these results in postmenopausal women. The Mediterranean diet pattern along with other healthy habits may help the primary prevention of bone, metabolic, and cardiovascular diseases in the postmenopausal period. It consists on the use of healthy foods that have anti-inflammatory and antioxidant properties, and is associated with a small but significant decrease in blood pressure, reduction of fat mass, and improvement in cholesterol levels. These effects remain to be evaluated over a longer period of time, with the assessment of hard outcomes such as bone fractures, diabetes, and coronary ischemia.
The purpose of this review was to assess recent evidence regarding the effects of low vitamin D levels on some highly prevalent clinical conditions of postmenopausal women. We reviewed and selected recent literature regarding menopause-related conditions associated with vitamin D deficiency and interventions to manage them. Low circulating 25-hydroxyvitamin D (25(OH)D) levels related to menopause are linked to diet, lifestyle, changes in body composition, insulin sensitivity, and reduced physical activity. Vitamin D supplementation increases serum 25(OH)D levels while normalizing parathyroid hormone and bone markers, and in women with serum 25(OH)D levels below 10 ng/ml supplementation may improve bone mineral density. Low vitamin D status has been associated with the metabolic syndrome, high triglyceride levels, and low high-density lipoprotein cholesterol levels. When compared with placebo, vitamin D supplementation may lower the risk of the metabolic syndrome, hypertriglyceridemia, and hyperglycemia. There is an inverse relationship between fat mass and serum 25(OH)D levels and, therefore, the dosage of supplementation should be adjusted according to the body mass index. Although vitamin D supplementation may improve glucose metabolism in prediabetic subjects, data regarding muscle strength are conflictive. There is evidence that vitamin D over-treatment, to reach extremely high circulating 25(OH)D levels, does not result in better clinical outcomes. The identification and treatment of vitamin D deficiency in postmenopausal women may improve their general health and health outcomes. Vitamin D supplementation should preferably be based on the use of either cholecalciferol or calcifediol.
- M J Page
- J E Mckenzie
- P M Bossuyt
Page MJ, McKenzie JE, Bossuyt PM et al. (2021) BMJ 372.