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Skeleton bones, distinguished by trabecular and cortical bone tissue content, exhibit varied growth and composition, in response to modified dietary calcium and phosphorus levels. The study investigated how gilts adapt their individual bone and bone region mineralisation kinetics in response to changing intake of Ca and P. A total of 24 gilts were fed according to a two-phase (Depletion (D) 60-95 and Repletion (R) 95-140 kg BW, respectively). During the D phase, gilts were fed either 60% (D60) or 100% (D100) of the estimated P requirement. Subsequently, during the R phase, half of the gilts from each D diet were fed either 100% (R100) or 160% (R160) of the estimated P requirement according to a 2 × 2 factorial arrangement. Bone mineral content (BMC) was assessed in the whole body, individual bones (femur and lumbar spine L2-L4), and bone regions (head, front legs, trunk, pelvis, femur, and hind legs) every 2 weeks using dual-energy X-ray absorptiometry (DXA). At 95 kg BW, gilts fed D60 showed reduced BMC and BMC/BW ratio in all studied sites compared to those fed D100 (P < 0.001). During the depletion phase, the allometric BW-dependent regressions slopes for BMC of D100 gilts remained close to 1 for all sites and did not differ from each other. In contrast, the slopes were lower in D60 gilts (P < 0.05), with an 18% reduction in the whole body, except for the front and hind legs, femur, and pelvis, which exhibited higher reductions (P < 0.05). At 140 kg BW, BMC and BMC/BW ratio of all studied sites were similar in gilts previously fed D60 and D100, but higher in R160 than in R100 gilts (P < 0.05), except for front and hind legs. During the repletion phase, the allometric BW dependent regressions slopes for BMC were lower (P < 0.05) in R100 than in R160 gilts (for whole body -10%; P < 0.01) except for front and hind legs, femur, and pelvis. In conclusion, bone demineralisation and recovery followed similar trends for all measured body sites. However, the lumbar spine region was most sensitive whereas the hind legs were least sensitive. These data suggest that using bone regions such as the head and forelegs that can be collected easily at the slaughterhouse may be a viable alternative to whole body DXA measurement., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The review provides a historical perspective on the convergence of our understanding of the physiology and pathophysiology of bone, calcium, phosphorus, vitamin D, parathyroid hormone, and FGF-23 their impact on rickets.

Apparent calcium absorption, total bone mineral content and density, and mineral contents of the right femur were studied using a growing rat model. Twenty-four male Wistar rats were fed with diets based on extruded whole grain red (RSD) or white sorghum (WSD), and control diet (CD) up to 60 days. The animals fed with sorghum diets consumed less and gained less weight compared to those fed with CD, but the efficiency of all diets was similar. Calcium intake was lower in animals fed with sorghum diets, related to the lower total intake of these animals. Apparent calcium absorption in animals fed with RSD was lower than in those fed with CD (CD: 72.7%, RSD: 51.0%, WSD: 64.8%). No significant differences in bone mineral density of total body, spin, femur, distal femur, tibia and proximal tibia were observed among the groups. However, Ca and P contents in the right femur of the rats consuming RSD were lower, indicating a certain imbalance in the metabolism of these minerals.

Calcium intake during a growth spurt may influence bone mineral acquisition. However, no population-based cohort studies have examined the relationship between calcium intake and whole-body bone mineral acquisition in Japanese children. The present study investigated the relationship between calcium intake and whole-body bone mineral acquisition in community-dwelling children in a northeast region of Japan using dual-energy X-ray absorptiometry. The source population for the baseline survey comprised all school children in 4th through 6th grades (275 children; age range, 10-12 y) in the Shiokawa area of Kitakata City, Fukushima. We obtained complete information from 220 children (100 girls and 120 boys), and analyzed total body less head (TBLH) bone mineral content (BMC), TBLH areal bone mineral density (aBMD), and bone mineral apparent density (BMAD) as an estimate of volumetric bone density. The Food Frequency Questionnaire for the Prevention and Management of Osteoporosis was validated in a previous study and used to estimate dietary nutrient intake. At baseline, mean calcium intake was 641 mg/d in girls and 660 mg/d in boys. Calcium intake in boys showed a significant (p<0.05) relationship with TBLH BMC and TBLH aBMD at follow-up, and with changes in TBLH BMC, TBLH aBMD, and TB BMAD from baseline to follow-up. After adjusting for potential confounding factors including body weight, we found no significant relationships between calcium intake and bone mineral parameters. Further studies are needed to clarify whether calcium intake affects bone mineral acquisition during pubertal growth spurts in the Japanese population.

Lower maternal vitamin D status during lactation is a common health problem. The objectives of this study were to investigate the effects of maternal 25-hydroxycholecalciferol (25-OH-D 3 ) supplementation during lactation on maternal and neonatal bone health in a sow model. 32 Large White × Landrace sows were assigned randomly to one of two diets supplemented with 2000 IU/kg vitamin D 3 (ND) or 50 μg/kg 25-OH-D 3 (25-D). The experiment began on day 107 of gestation and continued until weaning on day 21 of lactation. Maternal 25-OH-D 3 supplementation significantly decreased milk n-6:n-3 PUFA ratio, which supported bone formation of piglets. Supplementation with 25-OH-D 3 altered bone turnover rate of sows and piglets, as evidenced by higher bone-specific alkaline phosphatase (BALP) concentration in serum. 25-D sows had significantly higher bone density and mechanical properties of tibias and femurs than ND sows. Calcium (Ca) absorption rate was higher in 25-D sows than ND sows, which was caused partially by the increased mRNA expressions of renal 1α-hydroxylase (CYP27B1) and duodenal vitamin D receptor (VDR), transient receptor potential vanilloid 6 (TRPV6), and calcium-binding protein D9k (CaBP-D9k). Maternal 25-OH-D 3 supplementation increased tibial and femoral Ca content by up-regulating Ca-related gene expression in kidney (CYP27B1), ileum (VDR and claudin-2), and colon (VDR and CaBP-D9k), thus, activating 1,25-dihydroxyvitamin D 3 [1,25-(OH) 2 -D 3 ]-dependent Ca transport in piglets. In conclusion, improved milk fatty acids and higher mRNA expressions of calcitropic genes triggered by maternal 25-OH-D 3 supplementation would be the potential mechanism underlying the positive effects of 25-OH-D 3 on maternal and neonatal bone health.

Calcium depletion is a valuable non-invasive tool for studying skeletal system disorders. A low calcium diet (LCD) was used to examine the pathophysiological characteristics and molecular mechanisms of osteoporotic damage in caged laying hens. Sixty 64-wk-old laying hens were randomly housed in single-bird cages, and the cages were divided into 2 treatments: fed a regular calcium diet (RCD, 3.69%) or a LCD (1.56%) for 8 wk. The diet-induced changes of serum bone remodeling indicators, bone strength, microstructure of the distal femur, and the gene expression profiling of keel bone were measured. Compared to RCD hens, LCD hens had higher activity of serum alkaline phosphatase and tartrate resistant acid phosphatase but lower serum calcium concentrations with reduced tibial and femoral mass, width, and strength (P < 0.05). In addition, LCD hens had greater densities of osteoclasts, osteoblasts, connective tissue cells, and osteoid in the trabecular bone (P < 0.05). The transcriptome analysis revealed that 563 unigenes were differentially expressed in keel bone between LCD and RCD hens. The Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed genes were mainly associated with the osteoporosis-related signaling pathways involved in the biological functions of the bone cellular and extracellular structural modulations. The real-time PCR analysis further confirmed that the LCD enhanced the mRNA expression of collagen type 1 alpha 2, integrin-binding sialoprotein and periostin, but inhibited sclerostin expression. These findings indicate that LCD hens have a higher bone turnover and micro-architectural damage compared to RCD hens. The results further evidence dietary supplement of calcium is a critical nutrient strategy for improving hen skeletal health., (© 2019 Poultry Science Association Inc.)

1. The current experiment was performed to elucidate the effects of degelatinised bone meal (DBM) in combination with different particle sizes of limestone or oyster shell on broiler performance, bone characteristics and digestive and plasma alkaline phosphatase (ALP) activity. 2. Treatments were applied as a 3 × 3 factorial arrangement with three sources of P (DCP, bone meal and DBM) and three particle sizes (50, 100 and 200 µm) of limestone. Chickens were given either DCP or DBM with oyster shell (523 µm), resulting in a total of 11 treatments with 5 replicates of 8 chicks. 3. Performance criteria were measured weekly. Tibia strength, ash, calcium (Ca) and phosphorus (P) content and plasma P and Ca concentration along with plasma and intestinal alkaline phosphatase (ALP) activity and P digestibility were measured on d 14 and 28. 4. Body weight and FCR were improved in chicks which were fed DBM or oyster shell in comparison to the DCP and limestone respectively ( P ≤ 0.05). Performance was influenced ( P ≤ 0.05) by particle size; with coarser particles BW and feed intake were increased ( P ≤ 0.05). Tibia shear force and P content were reduced ( P ≤ 0.001), whereas tibia shear energy, length, ash and Ca content were increased by substitution of DCP with DBM or bone meal ( P ≤ 0.001; P ≤ 0.05). A significant difference was observed in the tibia length between the chicks fed oyster shell or limestone with different particles ( P ≤ 0.05). Plasma P concentration was reduced in chicks were fed with DBM, bone meal and lower limestone particle size. Intestinal ALP activity was increased ( P ≤ 0.001) in chicks which were fed DBM, bone meal, oyster shell or coarse particles of limestone. The P digestibility in chicks fed bone meal was lower than that of those fed DBM or DCP ( P ≤ 0.01). Overall, gelatin removal from bone meal improved broiler bone characteristics through the P digestibility and intestinal ALP activity enhancement.

Background: Phosphorus (P) supply is essential for bone mineralisation. Reduced P may result in osteopenia, whereas excessive P may result in environmental impacts. The objective was to study the long-term effect of three dietary P levels on net bone mineralisation in growing-finishing pigs. Eighteen female pigs were fed low P (LP (4.1)), medium P (MP (6.2)) or high P (HP (8.9 g P kg -1 DM)) from 39.7 until 110 kg. Trabecular, cortical and overall bone mineral density (BMD), ash, calcium (Ca) and P were determined after slaughter., Results: The LP diet generally reduced the BMD, ash, Ca and P in all bones, though all measures were markedly lowered in femur compared with humerus. The trabecular BMD in LP pigs was only different in the distal section compared to the MP-fed pigs (P < 0.05). In addition, ash, Ca and P were lower in the proximal and distal sections. No significant effect of HP was seen. Conclusively, LP caused lower net bone mineralisation, mainly of femur. The trabecular tissue of the distal bones seems to be most metabolically active., Conclusions: The MP level was sufficient for net bone mineralisation. Femur is recommended for studying bone fragility whereas humerus seems useful to study increased P retention. © 2019 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2019 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Fermented milk products like yogurt or soft cheese provide calcium, phosphorus, and protein. All these nutrients influence bone growth and bone loss. In addition, fermented milk products may contain prebiotics like inulin which may be added to yogurt, and provide probiotics which are capable of modifying intestinal calcium absorption and/or bone metabolism. On the other hand, yogurt consumption may ensure a more regular ingestion of milk products and higher compliance, because of various flavors and sweetness. Bone mass accrual, bone homeostasis, and attenuation of sex hormone deficiency-induced bone loss seem to benefit from calcium, protein, pre-, or probiotics ingestion, which may modify gut microbiota composition and metabolism. Fermented milk products might also represent a marker of lifestyle promoting healthy bone health.

Calcium is essential for normal bone growth and development. Inadequate calcium intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit signaling plays an important role in regulating bone homeostasis. Mice with c-Kit mutations are osteopenic. The present study aimed to investigate whether impairment of or reduction in c-Kit signaling affects bone turnover during calcium deprivation. Three-week-old male WBB6F1/J-Kit W /Kit W-v /J (W/W v ) mice with c-Kit point mutation, Kit W-sh /HNihrJaeBsmJ (W sh /W sh ) mice with an inversion mutation in the regulatory elements upstream of the c-Kit promoter region, and their wild-type controls (WT) were fed either a normal (0.6% calcium) or a low calcium diet (0.02% calcium) for 3 weeks. μCT analysis indicated that both mutants fed normal calcium diet had significantly decreased cortical thickness and cancellous bone volume compared to WT. The low calcium diet resulted in a comparable reduction in cortical bone volume and cortical thickness in the W/W v and W sh /W sh mice, and their corresponding controls. As expected, the low calcium diet induced cancellous bone loss in the W/W v mice. In contrast, W sh /W sh cancellous bone did not respond to this diet. This c-Kit mutation prevented cancellous bone loss by antagonizing the low calcium diet-induced increase in osteoblast and osteoclast numbers in the W sh /W sh mice. Gene expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the W sh mutation suppressed these effects. Our findings indicate that although calcium restriction increased bone turnover, leading to osteopenia, the decreased c-Kit expression levels in the W sh /W sh mice prevented the low calcium diet-induced increase in cancellous bone turnover and bone loss but not the cortical bone loss.

Purpose of Review: The purpose of this review is to provide an overview of dietary phosphorus, its sources, recommended intakes, and its absorption and metabolism in health and in chronic kidney disease and to discuss recent findings in this area with a focus on the effects of inorganic phosphate additives in bone health., Recent Findings: Recent findings show that increasing dietary phosphorus through inorganic phosphate additives has detrimental effects on bone and mineral metabolism in humans and animals. There is new data supporting an educational intervention to limit phosphate additives in patients with chronic kidney disease to control serum phosphate. The average intake of phosphorus in the USA is well above the recommended dietary allowance. Inorganic phosphate additives, which are absorbed at a high rate, account for a substantial and likely underestimated portion of this excessive intake. These additives have negative effects on bone metabolism and present a prime opportunity to lower total phosphorus intake in the USA. Further evidence is needed to confirm whether lowering dietary phosphorus intake would have beneficial effects to improve fracture risk.

Two experiments were conducted to determine the influence of dietary Ca concentrations (Experiment 1) and a combination of dietary Ca and non-phytate phosphorus (NPP) to create distinct Ca-to-NPP ratios (Experiment 2) in corn-soybean meal diets fed to broiler chickens from 2 to 23 d of age. In Experiment 1, dietary treatments consisted of 7 concentrations of Ca (0.4, 0.6, 0.8, 1.0, 1.2, 1.4, or 1.6% of the diet; 7 treatments total), and NPP concentrations were maintained at 0.3%. Increasing the dietary Ca concentration while maintaining 0.3% NPP elicited linear reductions (P < 0.01) in overall growth performance and tibia ash. Dietary effects also were observed for apparent retention of P and Ca, which decreased (P < 0.05) linearly or quadratically for birds receiving dietary treatments with Ca concentrations greater than 0.6%. In Experiment 2, diets were formulated to contain 3 concentrations of Ca (0.4, 1.0, or 1.6% of the diet) with NPP concentrations either constant at 0.45% or adjusted to maintain a dietary Ca-to-NPP ratio of 2:1 (6 treatments total). Growth performance was not influenced by Ca concentration or the Ca-to-NPP ratio. Tibia break force was lower (P < 0.01) in birds fed diets containing 0.4% Ca, regardless of the NPP concentration. Tibia ash increased (P < 0.01) as the dietary Ca concentration increased. Neither the dietary Ca nor NPP concentrations affected nitrogen retention (P > 0.05). Upon maintaining a constant 2:1 Ca-to-NPP ratio, P and Ca retention decreased (P < 0.01) at the highest Ca concentration. In conclusion, imbalanced Ca and NPP adversely influenced growth performance and nutrient retention of broilers, indicating the concentrations of Ca and NPP required to maximize bone structure and function may be higher than those required for performance., (© 2017 Poultry Science Association Inc.)

Most metabolic effects following bariatric surgery are favorable. One area in which the consequences seem to be detrimental is on skeletal health. Mechanisms that have been cited include malabsorption of calcium and vitamin D, decrease in mechanical loading, and changes in gastrointestinal and fat-derived hormone levels. It is important that the impact of these procedures on bone metabolism is closely examined. The significance of the bone loss that occurs, and its possible effect on future fracture risk, should also be evaluated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Magnesium, phosphorus, zinc, calcium, potassium and protein all play integral roles in maintaining bone health in adults; however, less is known about the importance of these minerals in utero. We aimed to determine associations between maternal dietary consumption of these nutrients during gestation and birth measures in offspring. Of 475 pregnant women recruited from a single antenatal clinic before 16-week gestation (2002-2003) as part of the vitamin D in pregnancy study, 346 with recorded maternal dietary intakes at 28- to 32-week gestation and offspring measures at birth were included. At birth, trained personnel measured the infant's weight, knee-heel length, crown-heel length and head circumference. At age 11, returning offspring underwent assessment of bone mass by dual-energy X-ray absorptiometry (n = 171). Crown-heel length was positively and weakly correlated with maternal intakes of all measured nutrients except calcium, fat and carbohydrate (r = 0.15-0.17; all p ≤ 0.05). The associations with protein, phosphorus and potassium were not attenuated after adjustment for maternal and offspring characteristics. No sustained associations were seen with other birth measures. Further, associations with some nutrients persisted with offspring height at age 11 years. Offspring bone area was associated with maternal diet, but no other measure of bone mass at age 11. After adjustment for height, associations were not significant. These data highlight that whilst some nutritional factors during pregnancy are associated with offspring linear growth in utero and childhood, this does not necessarily translate into an effect on offspring bone measures in childhood.

Introduction: The objective of the study was to assess dietary calcium intake in the Polish population and its influence on selected parameters of bone tissue., Materials and Method: 1,129 osteoporosis treatment-naive subjects, aged 20-80 years, randomly selected, were involved in the study. Bone status was established using densitometry of spine and hip and quantitative ultrasound of the calcaneus. Dietary calcium intake was calculated according to data gathered in a questionnaire., Results: Median calcium intake was 746 mg; 72% of subjects had calcium intake below the recommended dose. Calcium intake correlated negatively with age (r = -0.15; p<0.001) and positively with BMD in the spine (r = 0.06; p<0.05) and in the femoral neck (r = 0.07; p < 0.05). In subjects with the lowest calcium intake, a significantly lower femoral neck BMD and heel stiffness was noticed than in subjects with the highest calcium intake. However, multiple regression analysis showed that dietary calcium was not a predictor of low BMD, both in the hip and spine, as well as of bone stiffness in contrast to age, low BMI and female gender (p<0.0001). In all factors regression analysis, a weak influence of calcium intake on BMD was shown only in the subgroup of premenopausal women (β = 0.1; p<0.05)., Conclusions: In most subjects, dietary calcium intake was below the recommended dose; however, its influence on bone seems to be weak, except for persons with the greatest deficiency of dietary calcium and the subgroup of premenopausal women.

Increasing dietary Ca intake may prevent the excessive mobilisation of bone mineral in nursing mothers. We aimed to investigate whether higher Ca intake could positively modulate the bone mineral changes in Chinese postpartum lactating women. The study was a 12-month randomised, double-blinded, parallel group trial conducted over 12 months. A total of 150 postpartum women were randomly selected to receive either 40 g of milk powder containing 300 mg of Ca and 5 μg of vitamin D (Low-Ca group) or same milk powder additionally fortified with 300 mg of Ca (Mid-Ca group) or 600 mg of Ca (High-Ca group). Bone mineral density (BMD) for the whole body, the lumbar spine, the total left hip and its sub-regions was measured using dual-energy X-ray absorptiometry. A total of 102 subjects completed the whole trial. The duration of total lactating time was 7·9 (SD 2·8) months on average. The intention-to-treat analysis yielded the following mean percentage changes in BMD for the whole body, the lumbar spine and the total left hip, respectively: -0·93 (SD 1·97), 2·11 (SD 4·90) and -1·60 (SD 2·65)% for the Low-Ca group; -0·56 (SD 1·89), 2·21 (SD 3·77) and -1·43 (SD 2·30)% for the Mid-Ca group; and -0·44 (SD 1·67), 2·32 (SD 4·66) and -0·95 (SD 4·08)% for the High-Ca group. The differences between the groups were not statistically significant (P: 0·5-0·9). The results of the complete case analysis were similar. In sum, we found no significant differences in the bone mineral changes from baseline to 12 months in postpartum lactating women consuming milk powder fortified with different levels of Ca.

Background: Early Antarctic expeditions were plagued by nutrient deficiencies, due to lack of fresh food and reliance on preserved foods. Modern Antarctic expeditioners also require provisions to be shipped in, but improved knowledge and storage options ensure foods are nutritionally sound. Despite this, nutritional imbalances are observed., Objectives: To determine the adequacy of dietary intake of Antarctic expeditioners, with reference to bone health., Design: Dietary intake was determined on 225 adults (mean age 42±11 years, 16% female) during 12-month deployments at Australian Antarctic stations from 2004 to 2010, using weighed 3-day food records. Nutrient intake was analysed using FoodWorks. Foods were divided into the 5 food groups according to the Australian Guide to Healthy Eating., Results: Men consumed below the recommended levels [recommended daily intake (RDI)/adequate intakes (AI)] of calcium (79±42% of RDI, p<0.001), magnesium (83±34% of RDI, p<0.001), potassium (86±29% of AI, p<0.001) and fibre (75±30% of AI, p<0.001), and above the upper limit (UL) for sodium (125±48% of UL p<0.001), whereas women consumed below the recommended levels of calcium (68±21% of RDI, p<0.001) and iron (73±37% of RDI, p<0.001). Vitamin D intake is not substantial (<150 IU/d). Men consumed more alcohol than women (18±24 g/d vs. 10±13 g/d, p<0.05), nearer the guideline of ≤20 g/d. Men and women consumed approximately 1 serving of dairy food per day, and 3 of 5 recommended vegetable servings. Discretionary foods were consumed in excess of recommended., Conclusions: Improving consumption of calcium-rich (dairy) foods better supports bone health during sunlight deprivation. Increasing vegetable intake to recommended levels will increase fibre, potassium and magnesium intakes. The challenge is the logistics of providing these foods throughout the year.

A better understanding of the fate of dietary P use by growing pigs will allow an optimization of P use and enhance sustainable practices. The optimization of P utilization is complicated by the multiple criteria, such as growth performance, bone mineralization, and manure P used for assessment of needs. Mathematical modeling is a useful tool to describe relevant biological mechanisms and predict relationships that describe the whole system behavior. Modeling allows development of robust multicriteria approaches to optimize P utilization, feeding cost, and manure application cost. This paper describes and evaluates a model developed to simulate the fate of dietary P, that is, to simulate its digestive and metabolic utilization through digestion, soft tissue, and ash modules. The digestion module takes into account the varied sources of dietary minerals including responses to microbial and plant phytase and Ca and P interactions and predicts absorption and fecal excretion. The soft tissue module simulates the growth of the protein and is based on InraPorc model principles. The ash module simulates the partitioning of absorbed Ca and P into the bone, protein, and lipid compartments as well as urinary excretion. Model behavior showed that the model was able to accurately represent the impact of Lys deficiency on P retention, of Ca and P imbalances, and of Ca and P depletion and repletion sequences. The model's prediction capabilities in simulating whole-body protein, Ca, P, and ash based on published data showed high accuracy, with a slope and intercept that did not differ from 1 and 0, respectively, and an error due to disturbance (ED; variance not accounted for by regression of observed on predicted values). The model's prediction capabilities in simulating balance trial data showed good accuracy for apparent total tract digestibility (ATTD) of P (observed = -0.77 + 1.06 predicted) and P retention coefficient (observed = -4.5 + 1.15 predicted) with an ED of 89% for both criteria. The model's prediction capabilities in simulating Ca ATTD and Ca retention coefficient are lower (ED of 88 and 28%, respectively). This model simulates body ash independently of body protein and accounts for the impact of past and current dietary Ca and P supply. That ability is essential for the real-time adaptation of mineral supplies to suit individual production objectives, which would contribute to the overall success of pig production.

Calcium intake and absorption is important for bone health. In a randomized double-blind cross-over trial, we investigated effects of adding chymosin to milk on the intestinal calcium absorption as measured by renal calcium excretion and indices of calcium homeostasis. The primary outcome of the study was 24-h renal calcium excretion that is considered a proxy measure of the amount of calcium absorbed from the intestine. We studied 125 healthy men and women, aged 34 (25-45) years on two separate days. On each day, a light breakfast was served together with 500 ml of semi-skimmed milk to which either chymosin or similar placebo was added. Compared with placebo, chymosin did not affect 24-h urinary calcium, calcium/creatinine ratio, plasma parathyroid hormone, calcitonin or ionized calcium levels. However, during the first 4 h after intake of milk with chymosin, urinary calcium-creatinine ratio was significantly increased (17%) compared with placebo. Stratification by daily calcium intake showed effect of chymosin in participant with a habitual intake above the median (>1,050 mg/day) in whom both urinary calcium and calcium/creatinine ratio were significantly increased compared with placebo. Effects did not depend on plasma 25-hydroxyvitamin D levels. Chymosin added to milk increases renal calcium excretion in the hours following intake without affecting plasma levels of calcium or calciotropic hormones. The effect most likely represents enhanced intestinal calcium absorption shortly after intake. Further studies are warranted on whether intake of milk-added chymosin may cause beneficial effects on bone. www.ClinicalTrials.gov no. NCT01370941.

We investigated the effects of dietary calcium (Ca) supplementation on bone metabolism, kidney mineral concentrations, and kidney function in rats fed a high-phosphorus (P) diet. Wistar strain rats were randomly divided into 4 dietary groups and fed their respective diets for 21 d: a diet containing 0.3% P and 0.5% Ca (C), a diet containing 1.5% P and 0.5% Ca (HP), a diet containing 0.3% P and 1.0% Ca (HCa), or a diet containing 1.5% P and 1.0% Ca (HPCa). Compared to the C group, the high-P diet increased serum parathyroid hormone concentration, markers of bone turnover, receptor activator of NF-κB ligand mRNA expression of the femur, kidney Ca and P concentrations, urinary N-acetyl-β-D-glucosaminidase activity, and urinary β2-microglobulin excretion, and decreased bone mineral content and bone mineral density of the femur and tibia. Dietary Ca supplementation improved the parameters of bone metabolism and kidney function in rats fed the high-P diet, while there were no significant differences in kidney Ca or P concentrations between the HP and HPCa groups. These results suggest that dietary Ca supplementation prevented the bone loss and decline in kidney function induced by a high-P diet, whereas dietary Ca supplementation did not affect kidney mineral concentrations in rats fed the high-P diet.

Calcium ion (Ca2+) is the only second messenger well recognized for the established biological role among various inorganic ions. When cellular Ca2+ controls diverse biological phenomena, it is regulated under exquisitely precise mechanisms. Many proteins have been identified as Ca2+ signal-regulating factors, and still new "players" are added to the repertory. In this review, we will focus on Ca2+ channels, Ca2+-binding proteins,and signaling pathways controlled by these Ca2+ signal-regulating proteins, in order to discuss on molecular bases, biological significance, and possible future developments of Ca2+ signaling.

High-protein (>30% of energy from protein or >1.2 g/kg/day) and moderately high-protein (22% to 29% of energy from protein or 1.0 to 1.2 g/kg/day) diets are popular for weight loss, but the effect of dietary protein on bone during weight loss is not well understood. Protein may help preserve bone mass during weight loss by stimulating insulin-like growth factor 1, a potent bone anabolism stimulator, and increasing intestinal calcium absorption. Protein-induced acidity is considered to have minimal effect on bone resorption in adults with normal kidney function. Both the quantity and predominant source of protein influence changes in bone with diet-induced weight loss. Higher-protein, high-dairy diets may help attenuate bone loss during weight loss., (Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

A variety of genetic, mechano-response-related, endocrine-metabolic, and nutritional determinants impact bone health. Among the nutritional influences, protein intake and dietary acid load are two of the factors most controversially discussed. Although in the past high protein intake was often assumed to exert a primarily detrimental impact on bone mass and skeletal health, the majority of recent studies indicates the opposite and suggests a bone-anabolic influence. Studies examining the influence of alkalizing diets or alkalizing supplement provision on skeletal outcomes are less consistent, which raises doubts about the role of acid-base status in bone health. The present review critically evaluates relevant key issues such as acid-base terminology, influencing factors of intestinal calcium absorption, calcium balance, the endocrine-metabolic milieu related to metabolic acidosis, and some methodological aspects of dietary exposure and bone outcome examinations. It becomes apparent that for an adequate identification and characterization of either dietary acid load's or protein's impact on bone, the combined assessment of both nutritional influences is necessary.

Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition.

Background/objectives: Previous studies in Gambian women with a low calcium intake have described decreases in whole-body and regional bone mineral content (BMC) and areal bone mineral density (aBMD) during the first year of lactation. The aim of this study was to examine whether these effects are reversed after lactation., Subjects/methods: Thirty-three Gambian women who had a previous dual-energy X-ray absorptiometry (DXA) scan at 52 weeks lactation (L52) were invited to participate in a follow-up study when neither pregnant nor lactating (NPNL) for ≥3 months and/or when 52 weeks postpartum in a subsequent lactation (F52). Whole body, lumbar spine and hip bone mineral were measured by DXA. Anthropometry and dietary assessments were also conducted. Repeated-measures analysis of covariance was used to determine differences from L52 at NPNL and F52., Results: Twenty-eight women were scanned at NPNL and 20 at F52. The mean±s.d. calcium intake of the 33 women at NPNL and F52 was 360±168 mg/day. BMC, aBMD and size-adjusted BMC (SA-BMC) at all sites were higher at NPNL than L52. Percent increases in SA-BMC (mean±s.e.m.) were significant (P<0.0001): whole body=2.7±0.4%; lumbar spine=4.9±1.0%; total hip=3.7±1.0%. There were no significant differences in any measurements between the two lactation time points (L52 and F52)., Conclusions: This study of Gambian women with low calcium intakes demonstrates that bone mineral mobilised during lactation is recovered after lactation. Successive periods of long lactation are not associated with progressive skeletal depletion.

Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total-body calcium. The source of this additional urinary calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD), which is correlated with the increase in urine calcium excretion. The decreased BMD also correlates with an increase in markers of bone turnover as well as increased fractures. In humans, it is difficult to determine the cause of the decreased BMD in hypercalciuric stone formers. To study the effect of hypercalciuria on bone, we utilized our genetic hypercalciuric stone-forming (GHS) rats, which were developed through successive inbreeding of the most hypercalciuric Sprague-Dawley rats. GHS rats excrete significantly more urinary calcium than similarly fed controls, and all the GHS rats form kidney stones while control rats do not. The hypercalciuria is due to a systemic dysregulation of calcium homeostasis, with increased intestinal calcium absorption, enhanced bone mineral resorption, and decreased renal tubule calcium reabsorption associated with an increase in vitamin D receptors in all these target tissues. We recently found that GHS rats fed an ample calcium diet have reduced BMD and that their bones are more fracture-prone, indicating an intrinsic disorder of bone not secondary to diet. Using this model, we should better understand the pathogenesis of hypercalciuria and stone formation in humans to ultimately improve the bone health of patients with kidney stones.

The current study compared the effects of milk, yogurt or whey on the bone strength, body composition and serum biomarkers. Forty 12-week-old female Sprague-Dawley rats were ovariectomized (OVX), and another nine rats received a sham operation (Sham-Cont). After a 1-week recovery period, the OVX rats were divided into four dietary groups: OVX-control group (OVX-Cont), 17% skimmed milk powder diet group (OVX-Milk), 17% powdered fermented milk diet group (OVX-Yogurt) and 12% whey powder and 6% whey protein extract diet group (OVX-Whey) (n=10 in each group). The protein, nitrogen, fat, calcium and phosphorus contents of the experimental diets were adjusted to be similar to the control diet (AIN-93M). Eighty-four days after the beginning of the experimental diet, the total bone mineral density and bone mineral contents of lumbar vertebrae were significantly higher in the OVX-Milk and OVX-Whey groups than in the OVX-Cont group. Furthermore, the level of 1alpha, 25-dihydroxyvitamin D3 [1alpha, 25(OH)2D3] was significantly lower, while the serum level of FGF23 was significantly higher in the OVX-Milk, OVX-Yogurt and OVX-Whey groups than in the OVX-Cont group. These findings suggest that milk and the dairy products could improve bone metabolism in a postmenopausal animal model at least partly through changing the balance between 1alpha, 25(OH)2D3 and FGF23., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Cinacalcet, the first calcimimetic to be approved for the treatment of secondary hyperparathyroidism (SHPT) in the chronic kidney disease patients, offers a novel therapeutic approach to SHPT. The aim of this meta-analysis is to access the efficacy and safety of cinacalcet on bone and mineral metabolism disorders in the dialysis patients with SHPT. Randomized controlled trials on cinacalcet combined with vitamin D and/or phosphate binders in the dialysis patients with SHPT were identified in Pubmed, Sciencedirect, and the Cochrane library. Data were analyzed with RevMan software. We compared the proportion of patients achieving the biochemical targets recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines and the incidence of adverse events between the cinacalcet and control groups. Six trials involving 2,548 patients were included. A greater proportion of patients in the cinacalcet group compared with the conventional group achieved the KDOQI targets. The relative risks (RRs) were parathyroid hormone (PTH) (RR = 3.51, 95 % CI: 2.38-5.17), calcium (RR = 2.04, 95 % CI: 1.76-2.37), phosphorus (RR = 1.15, 95 % CI: 0.83-1.60), and calcium-phosphorus product (Ca × P) (RR = 1.41, 95 % CI: 1.18-1.69), the number of patients simultaneously achieving the KDOQI targets for PTH + Ca × P was also greater (RR = 3.89, 95 % CI: 2.36-6.41), with p < 0.001 for each. The most common adverse events were nausea, vomiting, diarrhea, and hypocalcemia, which had a higher incidence in the cinacalcet group, but were usually mild to moderate in severity and transient. Compared with conventional therapy, treatment with cinacalcet results in more patients achieving KDOQI targets and offers an effective and safety therapeutic option for controlling mineral and bone disorders in the dialysis patients with SHPT.

Low calcium (Ca) intake is the one of risk factors for both bone loss and medial elastocalcinosis in an estrogen deficiency state. To examine the effect of different amounts of Ca intake on the relationship between bone mass alteration and medial elastocalcinosis, 6-wk-old female SD rats were randomized into ovariectomized (OVX) control or OVX treated with vitamin D(3) plus nicotine injection (VDN) groups. The OVX treated with VDN group was then divided into 5 groups depending on the different Ca content in their diet, 0.01%, 0.1%, 0.6%, 1.2%, and 2.4% Ca intakes. After 8 wk of experimentation, the low Ca intake groups of 0.01% and 0.1% showed a low bone mineral density (BMD) and bone properties significantly different from those of the other groups, whereas the high Ca intake groups of 1.2% and 2.4% showed no difference compared with the OVX control. Only in the 0.01% Ca intake group, a significantly higher Ca content in the thoracic artery was found compared with that of the OVX control. Arterial tissues of the 0.01% Ca intake group showed an increase of bone-specific alkaline phosphatase (BAP) activity, a marker of bone mineralization, associated with arterial Ca content. However, the high Ca intake did not affect arterial Ca content nor arterial BAP activity. These results suggested that a low Ca intake during periods of rapid bone loss caused by estrogen deficiency might be one possible cause for the complication of both bone loss and medial elastocalcinosis.

Calcium is the most abundant cation in the human body, of which approximately 99% occurs in bone, contributing to its rigidity and strength. Bone also functions as a reservoir of Ca for its role in multiple physiologic and biochemical processes. This article aims to provide a thorough understanding of the absorptive mechanisms and factors affecting these processes to enable one to better appreciate an individual's Ca needs, and to provide a rationale for correcting Ca deficiencies. An overview of Ca requirements and suggested dosing regimens is presented, with discussion of various Ca preparations and potential toxicities of Ca treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Factors affecting bone calcium deposition across pregnancy and lactation are not well characterized., Objective: The impact of maternal age, calcium intake, race-ethnicity, and vitamin D status on the rate of bone calcium deposition (VO+) was assessed across pregnancy and lactation., Design: Stable calcium isotopes were given to 46 women at pre- or early pregnancy (trimester 1), late pregnancy (trimester 3), and 3-10 wk postpartum. Three cohorts were included: 23 adolescents from Baltimore (MD), aged 16.5 ± 1.4 y (mean ± SD; Baltimore cohort); 13 adults from California, aged 29.5 ± 2.6 y (California cohort); and 10 adults from Brazil, aged 30.4 ± 4.0 y (Brazil cohort). The total exchangeable calcium pool, VO+, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25(OH)₂D], parathyroid hormone, and calcium intake were evaluated., Results: At trimester 3, inverse associations between 1,25(OH)₂D and VO+ were evident in the Baltimore (P = 0.059) and Brazil (P = 0.008) cohorts and in the whole group (P = 0.029); calcium intake was not a significant determinant of VO+ in any group during pregnancy. At postpartum, a significant positive association was evident between VO+ and calcium intake (P ≤ 0.002) and between VO+ and African ethnicity (P ≤ 0.004) in the whole group and within the Baltimore and Brazil cohorts., Conclusions: Elevated 1,25(OH)₂D was associated with decreased rates of bone calcium deposition during late pregnancy, a finding that was particularly evident in pregnant adolescents and adult women with low calcium intakes. Higher dietary calcium intakes and African ethnicity were associated with elevated rates of bone calcium deposition in the postpartum period.

Pregnancy and lactation are times of additional demand for Ca. Ca is transferred across the placenta for fetal skeletal mineralisation, and supplied to the mammary gland for secretion into breast milk. In theory, these additional maternal requirements could be met through mobilisation of Ca from the skeleton, increased intestinal Ca absorption efficiency, enhanced renal Ca retention or greater dietary Ca intake. The extent to which any or all of these apply, the underpinning biological mechanisms and the possible consequences for maternal and infant bone health in the short and long term are the focus of the present review. The complexities in the methodological aspects of interpreting the literature in this area are highlighted and the inter-individual variation in the response to pregnancy and lactation is reviewed. In summary, human pregnancy and lactation are associated with changes in Ca and bone metabolism that support the transfer of Ca between mother and child. The changes generally appear to be independent of maternal Ca supply in populations where Ca intakes are close to current recommendations. Evidence suggests that the processes are physiological in humans and that they provide sufficient Ca for fetal growth and breast-milk production, without relying on an increase in dietary Ca intake or compromising long-term maternal bone health. Further research is needed to determine the limitations of the maternal response to the Ca demands of pregnancy and lactation, especially among mothers with marginal and low dietary Ca intake, and to define vitamin D adequacy for reproductive women.

The consumption of fatty acids, nutrients, and regular physical activity, individually influence bone mechanical properties in rats. To investigate their effects in combination, male rats were divided into the seven groups: G1: regular food and drinking water; G2: same as Gr.1 + physical activity (Whole body vibration; WBV); G3: same as Gr.2 + Calcium, Vit. D, Boron; G4: same as Gr.3 + canola oil; G5: same as Gr.3 + sunflower oil; G6: same as Gr.3 + mix of sunflower oil and canola oil; and G7: same as Gr.3 + coconut oil; and treated for 8 weeks. Analysis between the control with the groups 2 and 3 revealed that vibration in the G2 increased the body weight (P = 0.04), with no other major difference in plasma and bone indices. Comparison between the control with the G4-G7 (the oil groups) revealed that the rats in the G5 had a lower body weight (15 % less) and a significant increase in plasma levels of Estradiol in the G7 was noted. In addition, levels of Testosterone in the G4 and G7, and Free Testosterone in the G7 had a remarkable increase. Similar trend was observed for plasma levels of Vit. D in the G4 and G5. The stiffness and the breaking strength of the femur in the G7, and the breaking strength of the lumbar in the G7 compared to the control and the G4 and G5 was significantly higher and tended to increase in comparison to the G6. Better and stronger measurements observed for coconut oil is warranted to further study its effect on biomechanical properties of bones.

A most common and trusted source of Ca is milk or other dairy products. However, some oriental people do not drink milk due to lactose indigestion and intolerance, which make them allergic to milk. There have been many studies on alternative calcium-rich diet or Ca supplements. Among them, teleost fish like anchovy and mola, which are commonly consumed in Asian countries, could be an important Ca dietary supplement, especially in population groups with low intakes of milk and dairy products. In this chapter, we summarize beneficial effects of teleost fish bone peptide (FBP) for Ca bioavailability and bone mineralization, based on our researches., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We have previously reported on a case-series of children (n=46) with suspected calcium-deficiency rickets who presented in The Gambia with rickets-like bone deformities. Biochemical analyses discounted vitamin D-deficiency as an aetiological factor but indicated a perturbation of Ca-P metabolism involving low plasma phosphate and high circulating fibroblast growth factor-23 (FGF23) concentrations. A follow-up study was conducted 5 years after presentation to investigate possible associated factors and characterise recovery. 35 children were investigated at follow-up (RFU). Clinical assessment of bone deformities, overnight fasted 2 h urine and blood samples, 2-day weighed dietary records and 24 h urine collections were obtained. Age- and season-matched data from children from the local community (LC) were used to calculate standard deviation scores (SDS) for RFU children. None of the RFU children had radiological signs of active rickets. However, over half had residual leg deformities consistent with rickets. Dietary Ca intake (SDS-Ca=-0.52 (0.98) p=0.04), dietary Ca/P ratio (SDS-Ca/P=-0.80 (0.82) p=0.0008) and TmP:GFR (SDS-TmP:GFR=-0.48 (0.81) p=0.04) were significantly lower in RFU children compared with LC children and circulating FGF23 concentration was elevated in 19% of RFU children. Furthermore an inverse relationship was seen between haemoglobin and FGF23 (R(2)=25.8, p=0.004). This study has shown differences in biochemical and dietary profiles between Gambian children with a history of rickets-like bone deformities and children from the local community. This study provided evidence in support of the calcium deficiency hypothesis leading to urinary phosphate wasting and rickets and identified glomerular filtration rate and iron status as possible modulators of FGF23 metabolic pathways., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The acquisition and maintenance of bone mass and strength are influenced by environmental factors, including physical activity and nutrition. Among micronutrients, calcium (Ca) and inorganic (i) phosphate (P) are the two main constituents of hydroxyapatite, the bone mineral that strengthens the mechanical resistance of the organic matrix. Bone contains about 99% and 80% of the body's entire supply of Ca and P, respectively. The Ca/P mass ratio in bone is 2.2, which is similar to that measured in human milk. The initial step of Ca-Pi crystal nucleation takes place within matrix vesicles that bud from the plasma membrane of osteogenic cells and migrate into the extracellular skeletal compartment. They are endowed with a transport system that accumulates Pi inside the matrix vesicles, followed by the influx of Ca ions. This process leads to the formation of hydroxyapatite crystal and its subsequent association with the organic matrix collagen fibrils. In addition to this structural role, both Ca and Pi positively influence the activity of bone-forming and bone-resorbing cells. Pi plays a role in the maturation of osteocytes, the most abundant cells in bone. Osteocytes are implicated in bone mineralization and systemic Pi homeostasis. They produce fibroblast growth factor-23, a hormonal regulator of renal Pi reabsorption and 1,25-dihydroxy vitamin D production. This relationship is in keeping with the concept proposed several decades ago of a bone-kidney link in Pi homeostasis. In contrast to their tight association in bone formation and resorption, Ca and Pi renal reabsorption processes are independent from each other, driven by distinct molecular machineries. The distinct renal control is related to the different extraskeletal functions that Ca and Pi play in cellular metabolism. At both the renal and the intestinal levels, interactions of Ca and Pi have been documented that have important implications in the acquisition and maintenance of bone health, as well as in osteoporosis management. In the kidney, increased Pi intake enhances Ca reabsorption and Ca balance. During growth and adulthood, administration of Ca-Pi in a ratio close to that of dairy products leads to positive effects on bone health. In contrast, when separately ingested as pharmaceutical salt supplements, thus inducing large differences between Ca and Pi concentrations in the intestinal lumen, they might have adverse effects on bone health. In osteoporotic patients treated with anabolic agents, a Ca-Pi supplement appears to be preferable to carbonate or citrate Ca salt. In conclusion, Ca and Pi constitute a key duo for appropriate bone mineral acquisition and maintenance throughout life. Outside the skeleton, their essential but distinct physiological functions are controlled by specific transporters and hormonal systems that also serve to secure the appropriate supply of Ca and Pi for bone health. Key teaching points: Bone contains about 99% and 80% of the body's supply of Ca and P, respectively, as hydroxyapatite and has a Ca/P mass ratio of about 2.2, close to that measured in human milk. The first step of Ca-Pi crystal nucleation takes place within matrix vesicles that bud from the plasma membrane of osteogenic cells. In addition to their structural role, both Ca and Pi influence bone-forming and bone-resorbing cells. There is a bone-kidney link in Pi homeostasis in which fibroblast growth factor-23, a molecule produced by osteocytes, appears to play a pivotal role. In contrast to their tight association during bone formation and resorption, both intestinal and renal Ca and Pi processes are independent of each other. Observational and interventional studies suggest that Ca-Pi salt or dairy products can exert positive effects on bone acquisition and maintenance.

The analysis of mice that lack systemically the actions of the active form of vitamin D, 1,25(OH)₂D, has shown that 1,25(OH)₂D is an essential regulator of calcium homeostasis and that its actions are aimed at maintaining serum calcium levels within narrow limits. Especially the stimulation of intestinal calcium transport by 1,25(OH)₂D is important for calcium and bone homeostasis. The involved transporters are however still elusive. The targeted deletion of 1,25(OH)₂D action in chondrocytes has provided compelling evidence for a paracrine control of bone development and endocrine regulation of phosphate homeostasis by 1,25(OH)₂D. Targeting vitamin D receptor (VDR) function in other tissues will further enhance our understanding of the cell-type specific action of 1,25(OH)₂D. In this review, we will discuss the current understanding and remaining questions concerning the calcemic actions of 1,25(OH)₂D in the intestine, kidney and bone, with special focus on the evidence obtained by the use of transgenic mouse models., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Context: Overweight adolescents have low bone mineral content for weight and are at increased risk for fractures., Objective: The aim was to determine whether overweight and obesity influence the positive relationship between dietary calcium intake and skeletal calcium retention in adolescents., Design: Analysis of pooled data from calcium balance studies in adolescents., Setting: Participants each underwent a 3-wk calcium balance study in a controlled environment., Participants: Participants included 280 White, Black, and Asian boys (n = 73) and girls (n = 207) ages 10-16 yr., Main Outcome Measure: The relationship among body mass index (BMI), calcium intake, and calcium retention was modeled using linear regression., Results: Calcium intake, BMI, sex, race, and age explained 27.9% of the variation in calcium retention. At low calcium intakes, there was no effect of BMI on skeletal calcium retention, but at higher calcium intakes, BMI increased skeletal calcium retention., Conclusions: Greater gains in calcium retention occur with increases in calcium intake in adolescents with higher BMI compared with those with lower BMI. Additional studies are needed to investigate whether increasing calcium intake reduces the increased risk of fracture associated with overweight and obesity in adolescents.

Adolescence is an important period of nutritional vulnerability due to increased dietary requirements for growth and development and special dietary habits. Calcium needs are elevated as a result of the intensive bone and muscular development and thus adequate calcium intake during growth is extremely important to reach the optimum peak bone mass and to protect against osteoporosis in the adult age, a major public health threat whose incidence is increasing in Western countries. However, most children and adolescents worldwide fail to achieve the recommended calcium intake. The hormonal changes associated with the pubertal period promote greater mineral utilization, which needs to be satisfied with suitable calcium consumption. Diet, therefore, must contribute nutrients in sufficient quality and quantity to allow maximum bone mass development. Consequently, adolescents should be educated and encouraged to consume adjusted and balanced diets that, together with healthy lifestyles, enable optimal calcium utilization.

Phosphorylation, internalization, and desensitization of G protein-coupled receptors, such as the parathyroid hormone (PTH) and PTH-related peptide (PTHrP) receptor (PTH1R), are well characterized and known to regulate the cellular responsiveness in vitro. However, the role of PTH1R receptor phosphorylation in bone formation and osteoblast functions has not yet been elucidated. In previous studies, we demonstrated impaired internalization and sustained cAMP stimulation of a phosphorylation-deficient (pd) PTH1R in vitro, and exaggerated cAMP and calcemic responses to s.c. PTH infusion in pdPTH1R knock-in mouse model. In this study, we examined the impact of impaired PTH1R phosphorylation on the skeletal phenotype of mice maintained on normal, low, and high calcium diets. The low calcium diet moderately reduced (P<0.05) bone volume and trabecular number, and increased trabecular spacing in both wild-type (WT) and pd mice. The effects, however, seem to be less pronounced in the female pd compared to WT mice. In primary calvarial osteoblasts isolated from 2-week-old pd or WT mice, PTH and PTHrP decreased phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2), a member of mitogen-activated protein kinase, and cyclin D1, a G₁/S phase cyclin, in vitro. In contrast to WT osteoblasts, down-regulation of cyclin D1 was sustained for longer periods of time in osteoblasts isolated from the pd mice. Our results suggest that adaptive responses of intracellular signaling pathways in the pd mice may be important for maintaining bone homeostasis.

The objective of the present study was to investigate the nutritional status from the aspect of bone metabolism in Japanese elite male athletes with increased bone resorption. Urinary levels of a bone resorption marker, cross-linked N-terminal telopeptide of type 1 collagen (NTX), were measured in 71 professional baseball players (age, 18-39 years); the mean urinary NTX level was 65.6 (range, 17.5-269.0) nM BCE/mM Cr. Of 71 athletes, 9 with high levels of urinary NTX (greater than mean + 1 SD) were examined by measuring serum biochemical markers and nutritional assessment (simple food frequency questionnaire). Serum biochemical marker analysis showed that 7 of these 9 athletes had vitamin D insufficiency, as indicated by low serum levels of 25-hydroxyvitamin D, and that all 9 athletes showed vitamin K insufficiency as indicated by low levels of vitamins K(1) and K(2). Nutritional assessment revealed high intakes of protein and low intakes of calcium and vitamin D based on adequate intake (AI). However, daily vitamin K intake achieved the AI. These results suggest that there exist elite male athletes who show increased bone resorption and calcium and vitamin D insufficiency. However, there was a discrepancy between vitamin K intake and serum levels of vitamins K(1) and K(2). The present study raised an issue regarding the nutritional status from the point of view of bone metabolism in elite male athletes such as professional baseball players.

Although the regulation of renal 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) is reasonably well understood, the same cannot be said about the regulation of bone CYP27B1 expression. We have compared the regulation of kidney and bone CYP27B1 expression with modulation of dietary vitamin D and calcium levels. Vitamin D-deplete and vitamin D-replete female Sprague-Dawley rats were fed either 1% Ca (HC) or 0.1% Ca (LC) diets from 6 months of age. At 9 months of age, animals were killed for mRNA analyses from kidney and bone by real-time RT-PCR. Additionally, primary bone cells were cultured from pCYP27B1-Luc reporter mice in pro-osteogenic media over 15 days and analysed for mRNA for CYP27B1 and other osteogenic markers. In vivo expression of bone CYP27B1 mRNA was independent of changes to kidney CYP27B1 levels with both serum 1,25D and PTH as negative determinants of bone CYP27B1 mRNA levels. Bone cells in pro-mineralising conditions significantly increased CYP27B1 promoter activity over 15 days (P<0.001) which preceded marked increases in alkaline phosphatase, osteocalcin and vitamin D receptor mRNA expression and mineral deposition. These findings confirm that the regulation of bone CYP27B1 is unique from that in the kidney, and may play an important role in bone formation., (Crown Copyright (c) 2010. Published by Elsevier Ltd. All rights reserved.)

Techniques for assessing bone dynamic are in high demand. Calcium (Ca) kinetic studies are currently being used in our clinical studies of bone turnover in adolescents and elderly. The technique has rarely been compared to the standard method of bone dynamic histomorphometry. We perturbed bone turnover through ovariectomy and sub-optimal dietary Ca in a female rat model to cross-calibrate Ca kinetics against dynamic histomorphometry. Kinetic studies involved oral and intravenous administration of (45)Ca and monitoring the tracer in blood, urine, feces, and bone over a 3-day period as part of a metabolic Ca balance study. Histomorphometric indices of mineral apposition rate, mineralizing surface, and bone formation rate were obtained from proximal metaphysis and mid-diaphysis region of tibial bone. Bone mineralization and resorption rates at the whole skeletal level as evaluated by kinetic studies were significantly correlated with the volume-based bone formation rate (BFR/BV) evaluated by dynamic histomorphometry in metaphyseal trabecular bone (r=0.72 and r=0.61, respectively, p<0.001) and surface-based bone formation rate (BFR/BS) in tibial cortex (r=0.63, p<0.001 and r=0.59, p<0.01, respectively). Significant correlations were also demonstrated between bone resorption and mineralization rates at the whole skeletal level (r=0.91, p<0.001) using (45)Ca kinetic data. Ca kinetic modeling showed an increase (p<0.001) in skeletal resorption and formation rates in response to ovariectomy (27.6 vs. 13.8 mg/d for bone resorption and 42.7 vs. 28 mg/d for bone formation in ovariectomized vs. their Sham-operated control animals, respectively). Ca kinetic data also showed that bone formation decreased by 30% and whole bone balance by 50%, when dietary Ca level was reduced from 0.4% to 0.2% (34.2 vs. 23.8 mg/d and 10.4 vs. 5.1 mg/d, respectively, p<0.001). Our data suggest that Ca kinetic studies can be used reliably to rapidly detect changes in bone turnover at the whole skeletal level in response to interventions., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Interventions other than medications in the management of osteoporosis are often overlooked. The purpose of this study was to investigate the association of physical activity and calcium intake with bone parameters., Methods: We measured the heel T-score and stiffness index (SI) in 1890 pre- and postmenopausal women by quantitative ultrasound (QUS) and assessed physical activity and dietary calcium intake by questionnaire. Participants were divided according to their weekly physical activity (sedentary, moderately active, systematically active) and daily calcium consumption (greater than or less than 800 mg/day)., Results: SI values were significantly different among premenopausal groups (p = 0.016) and between sedentary and systematically active postmenopausal women (p = 0.039). QUS T-scores in systematically active premenopausal women with daily calcium intake > 800 mg/day were significantly higher than those in all other activity groups (p < 0.05) independent of calcium consumption., Conclusions: Systematic physical activity and adequate dietary calcium intake are indicated for women as a means to maximize bone status benefits.

Lactose, a disaccharide in milk or dairy products, is known to promote calcium absorption. The enzyme lactase is needed to digest lactose. Although lactase is secreted normally in childhood, the secretion is decreased with growth, and the activity becomes lower in adulthood. When the activity of lactase is low, lactose passes intact the small intestine and reaches the large intestine, could cause unpleasantness such as diarrhea and stomach ache. This is called lactose intolerance. In this paper, we discuss promotion of calcium absorption by lactose, lactose intolerance, and bone health.

This brief review focuses on calcium balance and homeostasis and their relationship to dietary calcium intake and calcium supplementation in healthy subjects and patients with chronic kidney disease and mineral bone disorders (CKD-MBD). Calcium balance refers to the state of the calcium body stores, primarily in bone, which are largely a function of dietary intake, intestinal absorption, renal excretion, and bone remodeling. Bone calcium balance can be positive, neutral, or negative, depending on a number of factors, including growth, aging, and acquired or inherited disorders. Calcium homeostasis refers to the hormonal regulation of serum ionized calcium by parathyroid hormone, 1,25-dihydroxyvitamin D, and serum ionized calcium itself, which together regulate calcium transport at the gut, kidney, and bone. Hypercalcemia and hypocalcemia indicate serious disruption of calcium homeostasis but do not reflect calcium balance on their own. Calcium balance studies have determined the dietary and supplemental calcium requirements needed to optimize bone mass in healthy subjects. However, similar studies are needed in CKD-MBD, which disrupts both calcium balance and homeostasis, because these data in healthy subjects may not be generalizable to this patient group. Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.

Ca is not only essential for bone mineralisation, but also for regulation of extracellular and intracellular processes. When the Ca2+ intake is low, the efficiency of intestinal Ca2+ absorption and renal Ca2+ reabsorption is increased. This adaptive mechanism involves calcitriol enhancement via parathyroid hormone stimulation. Bone is also highly affected. Low Ca2+ intake is considered a risk factor for osteoporosis. Patients with renal lithiasis may be at higher risk of recurrence of stone formation when they have low Ca2+ intake. The role of dietary Ca2+ on the regulation of lipid metabolism and lipogenic genes in adipocytes might explain an inverse relationship between dairy intake and BMI. Dietary Ca2+ restriction produces impairment of the adipocyte apoptosis and dysregulation of glucocorticosteroid metabolism in the adipose tissue. An inverse relationship between hypertension and a low-Ca2+ diet has been described. Ca2+ facilitates weight loss and stimulates insulin sensitivity, which contributes to the decrease in the blood pressure. There is also evidence that dietary Ca2+ is associated with colorectal cancer. Dietary Ca2+ could alter the ratio of faecal bile acids, reducing the cytotoxicity of faecal water, or it could activate Ca2+-sensing receptors, triggering intracellular signalling pathways. Also it could bind luminal antigens, transporting them into mucosal mononuclear cells as a mechanism of immunosurveillance and promotion of tolerance. Data relative to nutritional Ca2+ and incidences of other human cancers are controversial. Health professionals should be aware of these nutritional complications and reinforce the dairy intakes to ensure the recommended Ca2+ requirements and prevent diseases.