1Division of Geriatric Medication, Leuven College Hospital, Herestraat 49, 3000 Leuven, Belgium
2Gerontology and Geriatrics Part, Division of Experimental Medication, Okay.U.Leuven, 3000 Leuven, Belgium
3Leuven College Centre for Metabolic Bone Ailments, 3000 Leuven, Belgium
1Division of Geriatric Medication, Leuven College Hospital, Herestraat 49, 3000 Leuven, Belgium
2Gerontology and Geriatrics Part, Division of Experimental Medication, Okay.U.Leuven, 3000 Leuven, Belgium
3Leuven College Centre for Metabolic Bone Ailments, 3000 Leuven, Belgium
3Leuven College Centre for Metabolic Bone Ailments, 3000 Leuven, Belgium
4Experimental Medication and Endocrinology, Division of Experimental Medication, Okay.U.Leuven, 3000 Leuven, Belgium
4Experimental Medication and Endocrinology, Division of Experimental Medication, Okay.U.Leuven, 3000 Leuven, Belgium
4Experimental Medication and Endocrinology, Division of Experimental Medication, Okay.U.Leuven, 3000 Leuven, Belgium
5Molecular Endocrinology Laboratory, Division of Molecular Cell Biology, Okay.U.Leuven, 3000 Leuven, Belgium
1Division of Geriatric Medication, Leuven College Hospital, Herestraat 49, 3000 Leuven, Belgium
6Centre for Well being Companies and Nursing Analysis, Okay.U.Leuven, 3000 Leuven, Belgium
7Research Centre for Musculoskeletal Rehabilitation, Division of Rehabilitation Sciences, Okay.U.Leuven, 3000 Leuven, Belgium
Summary
1. Introduction
Osteoporosis is a systemic skeletal illness characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent enhance in bone fragility [1]. Along with the age-related enhance within the danger of falling, this compromised bone power leads to an elevated fracture danger [2]. Key determinants of this age-related bone fragility are calcium consumption and ranges of vitamin D, which promotes intestinal calcium absorption [3]. In older people, low dietary calcium consumption and vitamin D deficiency are frequent due to much less daylight publicity, diminished capability of the pores and skin for vitamin D synthesis, insufficient vitamin D dietary consumption, or much less environment friendly intestinal absorption of vitamin D, leading to a unfavorable calcium steadiness. This stimulates the secretion of parathyroid hormone (PTH) and induces age-associated secondary hyperparathyroidism, which reinforces bone turnover and accelerates bone loss [4]. Moreover, vitamin D deficiency results in muscle weak spot and will increase the chance of falling [5], low bodily efficiency [6], and dynamic and postural instability [7].
Taken collectively, low serum calcium and vitamin D deficiency enhance fracture danger by enhancing bone metabolism in addition to by growing the chance of falling. Substitution with calcium and vitamin D reduces each bone loss and the chance of falling and is due to this fact really useful as first-line technique within the prevention and therapy of osteoporosis and osteoporotic fractures. Pointers usually apply this suggestion to each women and men, though most particular person trials and meta-analyses have solely or primarily included girls, with restricted information in males [8]. This paper evaluations the prevailing proof for the impact of calcium and vitamin D supplementation on bone mineral density (BMD), muscle power, and the chance of falls and fractures in males.
2. Impact of Calcium and Vitamin D on Secondary Hyperparathyroidism, Bone Mineral Density, and Bone Turnover
Each calcium and vitamin D dietary supplements reverse the age-associated secondary hyperparathyroidism in older people. This discount in serum PTH is bigger with mixed calcium and vitamin D supplementation than with vitamin D alone [3] and relies on baseline calcium steadiness, with the best impact of supplementation noticed in people with the bottom calcium consumption and/or vitamin D ranges [9]. Gender, nonetheless, apparently is an impartial determinant of serum vitamin D [10], and to maintain PTH inside the regular vary, girls appear to require larger ranges of vitamin D than males [11].
A lower in ranges of PTH is related to a rise in BMD, as has been demonstrated in a latest meta-analysis in additional than 40000 women and men aged 50 years and older [12]. On this meta-analysis of 24 trials reporting BMD as an consequence, 19 trials included solely girls, whereas 4 trials included women and men [13–16], and one trial included solely males [17]. Of the 5 trials that included males, two trials decided the distinction in bone loss between calcium in monotherapy (±750 mg per day) and placebo [13, 15], whereas the others in contrast calcium (500 mg to 1000 mg per day) plus vitamin D (500 IU to 1000 IU per day) with placebo [14, 16, 17]. Total, therapy with calcium plus vitamin D or with calcium alone was related to a considerably diminished charge of bone loss on the hip and backbone. No subgroup analyses had been carried out to guage the affect of intercourse on therapy impact on BMD, however in keeping with the general conclusion of this meta-analysis, diminished bone loss was seen in a lot of the research that included males [13–16]. Nevertheless, the one obtainable men-only trial couldn’t exhibit a discount of bone loss regardless of supplementation with 1000 mg calcium and 1000 IU vitamin D per day throughout three years [17]. This unfavorable consequence might mirror the excessive baseline dietary calcium consumption within the males included within the examine (1160 mg per day) in comparison with decrease doses of calcium within the different trials, reminiscent of a day by day dose of 700 mg calcium [14] or much less (550 mg [15]), supporting the idea that substitution remedy solely is smart when calcium steadiness is unfavorable.
The lower in PTH with calcium and vitamin D supplementation can be related to diminished bone turnover [15, 16]. Meier et al. noticed that calcium and vitamin D supplementation throughout winter prevented seasonal modifications in PTH and bone loss in each women and men, though the impact on bone turnover was stronger in girls. On this context, it needs to be famous that seasonal modifications of bone turnover markers are solely vital in girls and nearly absent in males [16].
3. Impact of Calcium and Vitamin D on Muscle Power and the Threat of Falls
Supplementation with calcium and vitamin D not solely reduces bone loss but in addition reduces the chance of falling by enhancing muscle power, muscle operate, and steadiness [7, 18, 19]. Vitamin D receptors (VDRs) are current in skeletal muscle cells and should account for these results [20, 21]. In a latest meta-analysis, vitamin D remedy (200–1000 IU per day) lowered the chance of falling with 14% (RR 0.86, 95% CI 0.79–0.93) in contrast with calcium or placebo [22]. On this meta-analysis of ten trials, the quantity wanted to deal with with vitamin D to forestall one fall was 15, and—though a dose of 800 IU vitamin D or higher was best—a considerably decrease fall danger was additionally seen with 400 IU [22].
In an earlier meta-analysis of eight double blind randomized managed trials, however, a 19% fall discount (RR 0.81, 95% CI 0.71–0.92) was solely noticed with a dose of a minimum of 700 IU vitamin D per day and a 23% fall discount (RR 0.77, 95% CI 0.65–0.90) with serum vitamin D concentrations of a minimum of 60 nmol/L (24 ng/mL), whereas lower than 700 IU vitamin D per day didn’t scale back fall danger (RR 1.10, 95% CI 0.89–1.35) [23]. Subgroup analyses had been unable to doc a major discount in falls in males however the subset was small (N = 211) and the analyses underpowered. In an earlier meta-analysis of the impact of vitamin D on falls, sex-specific subgroup analyses recommended that the fall-preventing impact of vitamin D is impartial of intercourse: vitamin D diminished the chances ratio of falling in males by 21% (OR 0.79, 95% CI 0.57–1.1; P = 0.17) and in girls by 19% (OR 0.81, 95% CI 0.65–1.00; P = 0.05). Once more, the results of the sex-specific subgroup evaluation in males was not vital as a result of small variety of males within the included trials, however numerically just like the discount seen in girls [24].
Future analysis ought to decide the optimum dose of vitamin D to forestall falls, however obtainable proof means that males profit to the same extent as girls.
4. Antifracture Efficacy of Calcium and Vitamin D – “calcium benefits men”
A unfavorable calcium steadiness contributes to fracture danger by enhancing bone degradation via secondary hyperparathyroidism and by growing the chance of falling via a unfavorable impact on muscle power, muscle operate, and steadiness. Substitution with calcium and vitamin D is due to this fact thought-about the first-line technique within the prevention of osteoporotic fractures. To determine the antifracture efficacy of substitution, a number of particular person trials and meta-analyses have been carried out with calcium or vitamin D alone or mixed calcium plus vitamin D.
5. Security Issues about Supplementation
Whereas (conventionally dosed) vitamin D has not been related to security considerations, a latest meta-analysis has supplied proof to counsel that calcium dietary supplements (with out coadministered vitamin D) might probably be related to cardiovascular dangers. This security concern might probably be much more of a problem in males than in girls. Nevertheless, within the meta-analysis, sex-specific subgroup evaluation confirmed this elevated cardiovascular danger to be impartial of intercourse [41]. Though these findings represent a security sign that needs to be taken significantly, the information need to be interpreted with some warning. When dietary consumption was taken into consideration, there was no vital correlation between calcium consumption and danger of infarction. As well as, there was no impact of calcium on strokes or loss of life, not one of the trials had adjudicated cardiovascular outcomes in a standardized method, and the statistical consequence was solely borderline vital. Lastly, there are quite a few massive research of calcium plus vitamin D which have proven no elevated danger of cardiovascular occasions [31, 42] and research of calcium alone that didn’t present proof of an elevated cardiovascular danger with day by day supplemental consumption of 1200 mg calcium in girls [43] or 1000 mg calcium in males [44]. Nonetheless, reassessment of the function of calcium dietary supplements to forestall osteoporotic fractures is warranted. As a result of, basically, males are extra prone to coronary heart illness than girls, future research with dietary supplements ought to embrace cardiovascular endpoints and thoroughly assess security in males.
6. Conclusion
Age-associated bone loss as a consequence of secondary hyperparathyroidism and an elevated danger of falling are key determinants of osteoporosis and osteoporotic fractures. Substitution with calcium and vitamin D reduces bone loss by reversing secondary hyperparathyroidism and prevents falls by enhancing muscle power, muscle operate, and steadiness. In consequence, calcium and vitamin D supplementation is mostly really useful within the prevention of osteoporotic fractures. In males, information on the impact of calcium and vitamin D dietary supplements on BMD and the chance of falls and fractures are restricted. Nevertheless, from the mechanism of bone loss and from the obtainable proof, there isn’t a motive to imagine that males would reply in a different way to calcium and vitamin D supplementation in comparison with girls. Mixed supplementation with 1000 to 1200 mg calcium and 800 IU vitamin D per day needs to be notably thought-about in older or institutionalized males, males receiving glucocorticoids, and in male osteoporosis sufferers on antiresorptive or anabolic medicine.