Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: −0·038, n 22) and OC (MD: −0·610, n 24) with high heterogeneity and uNTX (MD: −8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 μg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

The transition towards more plant-based diets may pose risks for bone health such as low vitamin D and Ca intakes. Findings for the contribution of animal and plant proteins and their amino acids (AA) to bone health are contradictory. This 6-week clinical trial aimed to investigate whether partial replacement of red and processed meat (RPM) with non-soya legumes affects AA intakes and bone turnover and mineral metabolism in 102 healthy 20–65-year-old men. Participants were randomly assigned to diet groups controlled for RPM and legume intake (designed total protein intake (TPI) 18 E%): the meat group consumed 760 g RPM per week (25 % TPI) and the legume group consumed non-soya legume-based products (20 % TPI) and 200 g RPM per week, the upper limit of the Planetary Health Diet (5 % TPI). No differences in bone (bone-specific alkaline phosphatase; tartrate-resistant acid phosphatase 5b) or mineral metabolism (25-hydroxyvitamin D; parathyroid hormone; fibroblast growth factor 23; phosphate and Ca) markers or Ca and vitamin D intakes were observed between the groups (P > 0·05). Methionine and histidine intakes were higher in the meat group (P ≤ 0·042), whereas the legume group had higher intakes of arginine, asparagine and phenylalanine (P ≤ 0·013). Mean essential AA intakes in both groups met the requirements. Increasing the proportion of non-soya legumes by reducing the amount of RPM in the diet for 6 weeks did not compromise bone turnover and provided on average adequate amounts of AA in healthy men, indicating that this ecologically sustainable dietary change is safe and relatively easy to implement.

Both genetic selection and increasing nutrient density for improving growth performance had inadvertently increased leg problems of meat ducks, which adversely affects animal welfare. We hypothesised that slowing weight gain with improving tibia quality probably enhanced tibial mechanical properties and alleviated leg deformities. Therefore, the present study aimed to evaluate the effect of graded Ca supplementation in a low-nutrient density (LND) diet on tibia composition and bone turnover in meat ducks. A total of 720 15-d-old male meat ducks were randomly assigned and fed a standard nutrient density positive control (PC) diet containing 0·9 % Ca, and four LND diets with 0·5, 0·7, 0·9 and 1·1 % Ca, respectively. Ducks fed the 0·5 % Ca LND diet and the PC diet had higher incidence of tibial dyschondroplasia (TD). When compared with the 0·5 % Ca LND diet, LND diets with ≥0·7 % Ca significantly improved tibia composition, microarchitecture and mechanical properties, and consequently decreased the incidence of TD. Furthermore, LND diets with ≥0·7 % Ca increased osteocyte-specific gene mRNA expression, blocked the expression of osteoblast differentiation marker genes including osteocalcin, collagenase-1 and alkaline phosphatase (ALP), and also decreased the expression of osteoclast differentiation genes, such as vacuolar-type H+-ATPase, cathepsin K and receptor activator of NF-κB. Meanwhile bone markers such as serum ALP, osteocalcin (both osteoblast markers) and tartrate-resistant acid phosphatase (an osteoclast marker) were significantly decreased in at least 0·7 % Ca treated groups. These findings indicated that LND diets with ≥0·7 % Ca decreased bone turnover, which subsequently increased tibia quality for 35-d-old meat ducks.

Ca supplements are used for bone health; however, they have been associated with increased cardiovascular risk, which may relate to their acute effects on serum Ca concentrations. Microcrystalline hydroxyapatite (MCH) could affect serum Ca concentrations less than conventional Ca supplements, but its effects on bone turnover are unclear. In the present study, we compared the acute and 3-month effects of MCH with conventional Ca supplements on concentrations of serum Ca, phosphate, parathyroid hormone and bone turnover markers. We randomised 100 women (mean age 71 years) to 1 g/d of Ca as citrate or carbonate (citrate–carbonate), one of two MCH preparations, or a placebo. Blood was sampled for 8 h after the first dose, and after 3 months of daily supplementation. To determine whether the acute effects changed over time, eight participants assigned to the citrate dose repeated 8 h of blood sampling at 3 months. There were no differences between the citrate and carbonate groups, or between the two MCH groups, so their results were pooled. The citrate–carbonate dose increased ionised and total Ca concentrations for up to 8 h, and this was not diminished after 3 months. MCH increased ionised Ca concentrations less than the citrate–carbonate dose; however, it raised the concentrations of phosphate and the Ca–phosphate product. The citrate–carbonate and MCH doses produced comparable decreases in bone resorption (measured as serum C-telopeptide (CTX)) over 8 h and bone turnover (CTX and procollagen type-I N-terminal propeptide) at 3 months. These findings suggest that Ca preparations, in general, produce repeated sustained increases in serum Ca concentrations after ingestion of each dose and that Ca supplements with smaller effects on serum Ca concentrations may have equivalent efficacy in suppressing bone turnover.

For decades, it has been debated whether high protein intake compromises bone mineralisation, but no long-term randomised trial has investigated this in children. In the family-based, randomised controlled trial DiOGenes (Diet, Obesity and Genes), we examined the effects of dietary protein and glycaemic index (GI) on biomarkers of bone turnover and height in children aged 5–18 years. In two study centres, families with overweight parents were randomly assigned to one of five ad libitum-energy, low-fat (25–30 % energy (E%)) diets for 6 months: low protein/low GI; low protein/high GI; high protein/low GI; high protein/high GI; control. They received dietary instructions and were provided all foods for free. Children, who were eligible and willing to participate, were included in the study. In the present analyses, we included children with data on plasma osteocalcin or urinary N-terminal telopeptide of collagen type I (U-NTx) from baseline and at least one later visit (month 1 or month 6) (n 191 in total, n 67 with data on osteocalcin and n 180 with data on U-NTx). The level of osteocalcin was lower (29·1 ng/ml) in the high-protein/high-GI dietary group than in the low-protein/high-GI dietary group after 6 months of intervention (95 % CI 2·2, 56·1 ng/ml, P= 0·034). The dietary intervention did not affect U-NTx (P= 0·96) or height (P= 0·80). Baseline levels of U-NTx and osteocalcin correlated with changes in height at month 6 across the dietary groups (P< 0·001 and P= 0·001, respectively). The present study does not show any effect of increased protein intake on height or bone resorption in children. However, the difference in the change in the level of osteocalcin between the high-protein/high-GI group and the low-protein/high-GI group warrants further investigation and should be confirmed in other studies.

Suboptimal vitamin D status among the South Asian UK population is widely reported; however, its impact on bone health is unclear. The aim of the present study was to conduct a comparative investigation of vitamin D status in postmenopausal South Asian (SA) and Caucasian (C) women and its relationship to parathyroid hormone (PTH) concentration, biochemical markers of bone turnover and bone quality. A cross-sectional study of community-dwelling women aged 50–66 years was carried out. A total of sixty-six SA women of Pakistani origin and forty-two C women living in the same community were recruited. Fasting blood was taken for the measurement of vitamin D, PTH and biochemical markers of bone turnover, including type-1 collagen β C-telopeptide (βCTX), procollagen type-1 amino-terminal propeptide (P1NP), and bone-specific alkaline phosphatase (BAP) activity. Bone quality was assessed using broadband ultrasound attenuation (BUA). Total serum 25-hydroxyvitamin D (25(OH)D) was significantly lower in the SA women than the C women (medians: SA 10·5 v. C 47·1 nmol/l; P < 0·001) This was associated with a significantly elevated serum PTH concentration in the SA group (medians: SA 7·3 v. C 4·5 pmol/l; P < 0·01). BAP activity was also significantly higher in the SA group, indicating elevated osteoblast activity and bone turnover (medians: SA 23·0 v. C 20·0 U/l; P < 0·05). No significant differences were observed between the two groups for P1NP, βCTX or BUA. Although the SA women had significantly higher serum PTH and lower 25(OH)D concentrations than C women, this was not associated with significantly higher markers of bone resorption, or reduced bone quality in the SA women.

A randomised, parallel-design dietary intervention study was conducted in women (aged 45–75 years) with prehypertension or stage 1 hypertension. The aim was to compare the effects on bone turnover of a low-Na base-producing (LNAB) Dietary Approaches to Stop Hypertension (DASH)-type diet (including six serves lean red meat/week) with a high-carbohydrate low-fat (HCLF) diet with a higher acid load (both >800 mg dietary Ca/d). Fasting serum bone markers (baseline and week 14) and 24 h urinary electrolyte excretion (baseline, weeks 4, 8, 12 and 14) were measured. After the intervention period, the LNAB group (n 46) had a fall of 26 (sem 6) % (P < 0·0001) in urinary Na, an increase in K excretion (6·8 (sem 3·6) mmol/d; P = 0·07) and, compared with the HCLF group (n 49), a greater reduction in urinary Ca excretion by 0·7 (sem 0·3) mmol/d. Serum 25-hydroxyvitamin D, intact parathyroid hormone and osteocalcin did not change, and both groups had a similar increase of 23 (sem 5) % (P < 0·0001) in C-terminal telopeptide of type I collagen. The HCLF group had an 11 (sem 4) % increase (P = 0·003) in N-terminal propeptide, type I procollagen, which could indicate an increased rate of bone turnover. The fall in urinary Ca with the lower-Na lower-acid load diet is likely to have long-term beneficial effects on bone. As bone resorption was not different between the two dietary patterns with relatively high Ca intake, the effect on bone health of a dietary pattern with a lower acid load warrants further study on a lower Ca intake.

In adult bone, vitamin K contributes to bone health, probably through its role as co-factor in the carboxylation of osteocalcin. In children, the significance of vitamin K in bone-mass acquisition is less well known. The objective of this longitudinal study was to determine whether biochemical indicators of vitamin K status are related to (gains in) bone mineral content (BMC) and markers of bone metabolism in peripubertal children. In 307 healthy children (mean age 11·2 years), BMC of the total body, lumbar spine and femoral neck was determined at baseline and 2 years later. Vitamin K status (ratio of undercarboxylated (ucOC) to carboxylated (cOC) fractions of osteocalcin; UCR) was also measured at both time points. Markers of bone metabolism, sex steroids, vitamin D status and growth hormones were measured at baseline only. Large variations in the levels of the UCR were found at both time-points, indicating a substantial interindividual difference in vitamin K status. Improvement of vitamin K status over 2 years (n 281 children) was associated with a marked increase in total body BMC (r − 49·1, P < 0·001). The UCR was associated with pubertal stage, markers of bone metabolism, sex hormones and vitamin D status. A better vitamin K status was associated with more pronounced increase in bone mass in healthy peripubertal children. In order to determine the significance of these findings for childhood bone health, additional paediatric studies are needed.

Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk. In the absence of osteoporosis, risk preventive measures, particularly those modifying nutritional lifestyle, are appropriate. We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that, in the long term, may be expected to reduce postmenopausal bone loss. Thirty healthy postmenopausal women aged 59·3 (sd 3·3) years were enrolled in a prospective crossover trial of 16 weeks. After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk, participants were maintained during 6 weeks under the same 600 mg calcium diet and randomized to receive either 500 ml semi-skimmed milk, thus providing a total of 1200 mg calcium, or no milk supplement. In the next 6 weeks they were switched to the alternative regimen. At the end of the each period, i.e. after 4, 10 and 16 weeks, blood and urinary samples were collected. The changes in blood variables between the periods of 6 weeks without and with milk supplementation were: for parathyroid hormone, − 3·2 pg/ml (P = 0·0054); for crosslinked telopeptide of type I collagen, − 624 pg/ml (P < 0·0001); for propeptide of type I procollagen, − 5·5 ng/ml (P = 0·0092); for osteocalcin, − 2·8 ng/ml (P = 0·0014). In conclusion, a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion. This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis.

Severe vitamin D deficiency is common among Muslim immigrants. The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants. The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants. This 1-year-long randomised double-blinded placebo-controlled intervention with vitamin D3 (10 and 20 μg/d) included girls (10·1–14·7 years), women (18·1–52·7 years) and men (17·9–63·5 years) of Pakistani origin living in Denmark. The main endpoints were serum 25-hydroxyvitamin D (S-25OHD), parathyroid hormone, bone turnover markers and bone mass. The study showed that supplementation with 10 and 20 μg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women (4-fold), and that 10 μg increased S-25OHD concentrations 2-fold and 20 μg 3-fold in Pakistani men. S-25OHD concentrations increased at 6 months and were stable thereafter. Baseline S-25OHD concentrations tended to be lower in girls and women than in men; females achieved about 46 nmol/l and men 55 nmol/l after supplementation. Serum intact parathyroid hormone concentrations decreased at 6 months, but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine.

Recent cross-sectional data suggest that better vitamin K status in young girls (aged 3–16 years) is associated with decreased bone turnover, even though it is not associated with bone mineral content (BMC). The objective of the present study was to investigate the relationship between serum percentage of undercarboxylated osteocalcin (%ucOC), as an index of vitamin K status, and BMC and biochemical indices of bone turnover in peri-pubertal Danish girls. This peri-pubertal stage is a dynamic period of bone development, and as such, may represent an important window of opportunity for vitamin K status to modulate childhood bone health. Serum %ucOC and serum 25-hydroxyvitamin D (25 (OH) D) were measured at baseline in a study of 223 healthy girls aged 11–12 years. Urinary pyridinium crosslinks of collagen and serum total osteocalcin as markers of bone resorption and formation, respectively, as well as BMC (total body and lumbar spine) were also measured. Serum %ucOC (median 21·9 %) was not associated with markers of bone resorption or with total osteocalcin. Serum %ucOC was inversely correlated with serum 25 (OH) D (r − 0·143; P < 0·05). Serum %ucOC was negatively associated with BMC of the total body (β − 0·045; P < 0·001) and lumbar spine (β − 0·055; P < 0·05), after adjustment for potential confounders including vitamin D status. Better vitamin K status was associated with increased BMC, but not bone turnover, in healthy peri-pubertal Danish girls. There is a need for well-designed, randomized phylloquinone supplementation trials in children and adolescents to confirm epidemiological findings of an association between vitamin K status and bone health.

Crohn's disease is associated with osteoporosis, malnutrition and altered function of peripheral blood mononuclear cells (PBMC). The responses of circulating immune cells and extra-intestinal manifestations to increased inflammatory activity and to modulation by dietary supplementation are uncertain. The relationships between disease status, bone turnover and body mass and composition, PBMC function and fatty acid availability have been investigated in patients with Crohn's disease. The availability of n-3 and n-6 PUFA is altered in adult patients and interferon (IFN)-γ production by PBMC is lower. Increased inflammatory activity is associated with increased bone resorption in adult patients and decreased body mass in paediatric patients. In healthy male subjects there is a proportionate relationship between supplementary intake of EPA and DHA (0.3–2.0 g as fish oil/d) in combination with antioxidants (vitamins A, C and E and Se) and incorporation into plasma phospholipids and PBMC, and a non-linear relationship with PBMC synthesis of TNF-α, IL-6 and prostaglandin E2 (decrease) and IFN-γ (increase). In adults with Crohn's disease high-dose fish oil (2.7 g EPA+DHA/d) in combination with antioxidants (vitamins A, C and E and Se) increases the EPA and DHA content of PBMC and decreases the production of IFN-γ by PBMC, but is not associated with effects on bone turnover or nutritional status.

Osteoporosis is an important contributor to the global burden of disease, and in the UK alone results in one in three women and one in twelve men aged >50 years experiencing a fragility fracture. Optimising peak bone mass in early adulthood is thought to reduce osteoporosis risk by offsetting bone losses in later life. Ensuring sufficient vitamin D status (measured as 25-hydroxyvitamin D (25OHD) in plasma), among other factors, is believed to facilitate the achievement of optimum peak bone mass. Lower 25OHD is associated with a higher plasma concentration of parathyroid hormone (PTH). As PTH is associated with increased bone turnover and bone loss, maintenance of sufficient 25OHD is thought to have a protective effect on bone health. However, there is a lack of consensus internationally on what constitutes an optimum 25OHD concentration, and values between 30 and 80 nmol/l have been suggested. These values have been based on findings from various studies in adults in which PTH has been observed to plateau at a 25OHD concentration of >30 nmol/l; however, not all studies have found such a plateau. Although studies in younger adolescents (14–16 years) have shown an inverse relationship between PTH and 25OHD, the concentration of 25OHD required for achievement of optimum peak bone mass is unknown. The present review examines the evidence defining vitamin D insufficiency thresholds, and the relevance of such thresholds to adolescent bone health.

Physical activity (PA) is a popular therapy for the prevention and treatment of bone loss and osteoporosis because it has no adverse side effects, it is low cost, and it confers additional benefits such as postural stability and fall prevention. Bone mass is regulated by mechanical loading, and is limited but not controlled by diet. The mechanism by which strain thresholds turn bone remodelling ‘on’ and ‘off ’ is known as the mechanostat theory. Research in animals has shown that optimal strains are dynamic, with a high change rate, an unusual distribution and a high magnitude of strain, but the results of randomized controlled trials in human subjects have been somewhat equivocal. In the absence of weight-bearing activity nutritional or endocrine interventions cannot maintain bone mass. Biochemical markers of bone turnover predict bone mass changes, and findings from our research group and others have shown that both acute and chronic exercise can reduce bone resorption. Similarly, Ca intervention studies have shown that supplementation can reduce bone resorption. Several recent meta-analytical reviews concur that changes in bone mass with exercise are typically 2–3%. Some of these studies suggest that Ca intake may influence the impact of PA on bone, with greater effects in Ca-replete subjects. Comparative studies between Asian (high PA, low Ca intake) and US populations (low PA, high Ca intake) suggest that PA may permit an adaptation to low Ca intakes. Whether Ca and PA interact synergistically is one of the most important questions unanswered in the area of lifestyle-related bone health research.

Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72·2 (sd 6·4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0·05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0·05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0·05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0·887 ± 0·102 v. 1·104 ± 0·121 g/cm2; P < 0·01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.

We investigated the effect of wheat bran on biochemical indicators of Ca and bone metabolism in nineteen healthy women, aged 25·5 (se 0·9) years. Subjects received six wheat bran biscuits or six white flour biscuits per day for a period of 4 weeks (crossover). Wheat bran consumption increased fibre intake from 17·7 (se 1·3) to 29·6 (se 1·3) g/d (7 d food record) and enhanced P intake from 1225 (se 59) mg/d to 1663 (se 65) mg/d; P < 0·001. Mean daily Ca intake during wheat bran consumption (1110 (se 82) mg/d) significantly (P = 0·008) exceeded Ca ingestion during the white flour period (955 (se 67) mg/d). Wheat bran increased the number of defecations per week from 7·9 (se 0·8) to 12·2 (se 1·4) (P = 0·0018). Urinary Ca excretion over 24 h significantly (P = 0·021) decreased from 473 (se 53) μmol/mmol creatinine (control period) to 339 (se 37) μmol/mmol creatinine (wheat bran period). Serum 25-hydroxyvitamin D, 2 h fasting urinary Ca/creatinine excretions and 24 h urinary P excretion remained constant. No differences in serum levels of carboxy-terminal propeptide of type I procollagen (biomarker of bone formation) or in 2 h fasting urinary hydroxyproline/creatinine excretions (biomarker of bone resorption) were observed at the end of the two cycles of dietary supplementation. We conclude that a high fibre intake of approximately 30 g/d has no significant adverse effects on bone turnover in subjects with Ca intakes above 1000 mg/d and that the reduction in 24 h urinary Ca excretion is most probably the result of an adaptation process, induced by a decrease in net absorbed Ca.

An increase in dietary intake of B from 0.25 to 3.25 mg/d has been reported to increase plasma oestradiol and testosterone and decrease urinary Ca excretion in postmenopausal women. Consequently, it is suggested that the higher level of B intake could reduce bone loss associated with the menopause and cessation of ovarian function. The present study was designed to investigate the effect of a B supplement on bone mineral absorption and excretion, plasma sex steroid levels and urinary excretion of pyridinium crosslink markers of bone turnover in healthy postmenopausal volunteers. The women were accommodated in a metabolic unit, given a low-B diet (LBD; 0.33 mg/d) for 3 weeks and were asked to take a B supplement of 3 mg/d in addition to the LBD for a further 3 weeks. Changing B intake from 0.33 to 3.33 mg/d had no effect on minerals, steroids or crosslinks. However, the LBD appeared to induce hyperabsorption of Ca since positive Ca balances were found in combination with elevated urinary Ca excretion. This phenomenon may have inhibited or obscured any effect of B.