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This article discusses the importance of calcium balance in the bone response to exercise, particularly in preventing stress fractures in military populations, especially female recruits. The study used dual calcium isotope methodology to assess calcium kinetics in 21 healthy women during load carriage exercise or rest. The results showed that exercise increased total and fractional calcium absorption and improved calcium balance compared to rest. However, the study also highlighted the need for further research to understand calcium kinetics during exercise in different populations and modes of exercise, as well as the role of calcium intake and supplementation in the bone response to exercise. [Extracted from the article]

The article presents a study which assessed calcium balance after net acid excretion (NAE) as described in the acid-ash hypothesis in healthy adults. It is stated that the meta-analysis used superior methodological quality to examine calcium metabolism. The result of regression analysis to assess the dose-response relationship across the study subjects in terms of change of urinary calcium, calcium balance and marker of bone metabolism is revealed.

The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double-blind, placebo-controlled study, 52 men and women (mean age 65.2 ± 6.2 years) were randomly assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism, including intestinal fractional calcium absorption and calcium balance, obtained at baseline and at 6 months. At 6 months, net acid excretion was significantly lower in both treatment groups compared to placebo and it was negative, meaning subjects' dietary acid was completely neutralized (−11.3 mmol/d on 60 mmol/d; −29.5 mmol/d on 90 mmol/d, p < 0.001 compared to placebo). At 6 months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol/d (−46 ± 15.9 mg/d) and 90 mmol/d (−59 ± 31.6 mg/d) compared with placebo ( p < 0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/d compared to placebo (142 ± 80 mg/d on 90 mmol/d versus −80 ± 54 mg/d on placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/d, but this did not reach statistical significance ( p = 0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (−34.6 ± 39.1 ng/L on 90 mmol/d, p = 0.05; −71.6 ± 40.7 ng/L on 60 mmol/d, p = 0.02) whereas bone-specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/d group ( p = 0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer-term trials with definitive outcomes such as bone density and fracture are needed. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article focuses on a study of high and low salt intake in postmenopausal women. The discussion includes the effect of salt on calcium metabolism, the risk of calciuria and osteoporosis, controlled dietary intervention, stable isotope labeling techniques, data indicating calcium absorption and excretion, bone calcium balance, and biomarkers in blood and urine for bone resorption and growth.

The article discusses the results of a study that determined calcium requirements in Chinese-American boys and girls. The researchers used metabolic balance protocols and a range in calcium intakes to determine skeletal calcium retention in Chinese-American adolescents. The study found that boys had significantly higher bone turnover rate than girls at the same calcium intake. The researchers recommend that calcium requirements should be lowered for Chinese-American adolescents.

Vitamin D is an important factor in bone metabolism. Animal studies have shown a positive effect of vitamin D3 supplementation on fracture healing, but evidence from clinical trials is inconclusive. A randomized controlled trial was performed to assess the effects of vitamin D3 supplementation on fracture healing using HR‐pQCT–based outcome parameters. Thirty‐two postmenopausal women with a conservatively treated distal radius fracture were included within 2 weeks postfracture and randomized to a low‐dose (N = 10) and a high‐dose (N = 11) vitamin D intervention group receiving a 6‐week bolus dose, equivalent to 700 and 1800 IU vitamin D3 supplementation per day, respectively, in addition to a control group (N = 11) receiving no supplementation. After the baseline visit 1–2 weeks postfracture, follow‐up visits were scheduled at 3–4, 6–8, and 12 weeks postfracture. At each visit, HR‐pQCT scans of the fractured radius were performed. Cortical and trabecular bone density and microarchitectural parameters and microfinite element analysis–derived torsion, compression, and bending stiffness were assessed. Additionally, serum markers of bone resorption (CTX) and bone formation (PINP) were measured. Baseline serum levels of 25OHD3 were <50 nmol/L in 33% of all participants and <75 nmol/L in 70%. Compared with the control group, high‐dose vitamin D3 supplementation resulted in a decreased trabecular number (regression coefficient β: −0.22; p < 0.01) and lower compression stiffness (B: −3.63; p < 0.05, together with an increase in the bone resorption marker CTX (B: 0.062; p < 0.05). No statistically significant differences were observed between the control and low‐dose intervention group. In conclusion, the bolus equivalent of 700 U/day vitamin D3 supplementation in a Western postmenopausal population does not improve distal radius fracture healing and an equivalent dose of 1800 IU/day may be detrimental in restoring bone stiffness during the first 12 weeks of fracture healing. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Studies in healthy children have shown racial‐ethnic differences in bone markers and bone outcomes including fractures. At present, limited studies have evaluated the impact of race and ethnicity on bone markers and fractures within the pediatric chronic kidney disease (CKD) population. In a cohort study of 762 children between the ages of 1.5 years and 18 years, with CKD stages 1 to 4 from the CKD in children (CKiD) cohort, the relationship between racial‐ethnic group and bone markers (parathyroid hormone [PTH], 25‐hydroxyvitamin D [25‐OHD], 1,25‐dihydroxyvitamin D [1,25(OH)2D], and C‐terminal fibroblast growth factor [FGF23]) was determined using linear mixed models. Additionally, logistic regression was used to evaluate racial‐ethnic differences in prevalent fracture upon study entry. Black race was associated with 23% higher PTH levels (confidence interval [CI], 2.5% to 47.7%; p =.03), 33.1% lower 25‐OHD levels (CI, −39.7% to −25.7%; p <.0001), and no difference in C‐terminal FGF23 or 1,25(OH)2D levels when compared to whites. Hispanic ethnicity was associated with 15.9% lower C‐terminal FGF23 levels (CI, −28.3% to −1.5%; p =.03) and 13.8% lower 25‐OHD levels (CI, −22.2% to −4.5%; p =.005) when compared to whites. Black and Hispanic children had 74% (odds ratio [OR] 0.26; CI, 0.14 to 0.49; p =.001) and 66% (OR 0.34; CI, 0.17 to 0.65; p <.0001) lower odds of any fracture than white children at study entry, respectively. Race and ethnicity are associated with differences in bone markers and despite lower 25‐OHD levels, both black and Hispanic children with CKD reported a lower prevalent fracture history than white children. The current findings in the CKD population are similar to racial‐ethnic differences described in healthy children. Additional studies are needed to better understand how these differences might impact the management of pediatric CKD‐MBD. © 2020 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Serum calcium (Ca), bone biomarkers, and radiological imaging do not allow accurate evaluation of bone mineral balance (BMB), a key determinant of bone mineral density (BMD) and fracture risk. We studied naturally occurring stable (non‐radioactive) Ca isotopes in different body pools as a potential biomarker of BMB. 42Ca and 44Ca are absorbed from our diet and sequestered into different body compartments following kinetic principles of isotope fractionation; isotopically light 42Ca is preferentially incorporated into bone, whereas heavier 44Ca preferentially remains in blood and is excreted in urine and feces. Their ratio (δ44/42Ca) in serum and urine increases during bone formation and decreases with bone resorption. In 117 healthy participants, we measured Ca isotopes, biomarkers, and BMD by dual‐energy X‐ray absorptiometry (DXA) and tibial peripheral quantitative CT (pQCT). 44Ca and 42Ca were measured by multi‐collector ionization‐coupled plasma mass‐spectrometry in serum, urine, and feces. The relationship between bone Ca gain and loss was calculated using a compartment model. δ44/42Caserum and δ44/42Caurine were higher in children (n = 66, median age 13 years) compared with adults (n = 51, median age 28 years; p < 0.0001 and p = 0.008, respectively). δ44/42Caserum increased with height in boys (p < 0.001, R2 = 0.65) and was greatest at Tanner stage 4. δ44/42Caserum correlated positively with biomarkers of bone formation (25‐hydroxyvitaminD [p < 0.0001, R2 = 0.37] and alkaline phosphatase [p = 0.009, R2 = 0.18]) and negatively with bone resorption marker parathyroid hormone (PTH; p = 0.03, R2 = 0.13). δ44/42Caserum strongly positively correlated with tibial cortical BMD Z‐score (n = 62; p < 0.001, R2 = 0.39) but not DXA. Independent predictors of tibial cortical BMD Z‐score were δ44/42Caserum (p = 0.004, β = 0.37), 25‐hydroxyvitaminD (p = 0.04, β = 0.19) and PTH (p = 0.03, β = −0.13), together predicting 76% of variability. In conclusion, naturally occurring Ca isotope ratios in different body compartments may provide a novel, non‐invasive method of assessing bone mineralization. Defining an accurate biomarker of BMB could form the basis of future studies investigating Ca dynamics in disease states and the impact of treatments that affect bone homeostasis. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

The Cy/+ rat has been characterized as a progressive model of chronic kidney disease–mineral bone disorder (CKD‐MBD). We aimed to determine the effect of kidney disease progression on intestinal phosphorus absorption and whole‐body phosphorus balance in this model. A total of 48 Cy/+ (CKD) and 48 normal littermates (NL) rats were studied at two ages: 20 weeks and 30 weeks, to model progressive kidney function decline at approximately 50% and 20% of normal kidney function. Sodium‐dependent and sodium‐independent intestinal phosphorus absorption efficiency were measured by the in situ jejunal ligated loop method using 33P radioisotope. Our results show that CKD rats had slightly higher sodium‐dependent phosphorus absorption compared to NL rats, and absorption decreased from 20 to 30 weeks. These results are in contrast to plasma 1,25OH2D, which was lower in CKD rats. Gene expression of the major intestinal phosphorus transporter, NaPi‐2b, was not different between CKD and NL rats in the jejunum but was lower in CKD rats versus NL rats in the duodenum. Jejunal ligated loop phosphorus absorption results are consistent with percent net phosphorus absorption results obtained from metabolic balance: higher net percent phosphorus absorption values in CKD rats compared with NL, and lower values in 30‐week‐olds compared with 20‐week‐olds. Phosphorus balance was negative (below zero) in CKD rats, significantly lower in 30‐week‐old rats compared with 20‐week‐old rats, and lower in CKD rats compared with NL rats at both ages. These results demonstrate no reduction in intestinal phosphorus absorption with progression of CKD despite lower 1,25OH2D status when assessed by an in situ ligated loop test, which is in contrast to the majority of in vitro studies, and if confirmed in further studies, could challenge the physiological relevance of in vitro findings. © 2019 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: Previous studies found that dairy foods were associated with higher areal bone mineral density (BMD). However, data on bone geometry or compartment‐specific bone density is lacking. In this cross‐sectional study, the association of milk, yogurt, cheese, cream, milk+yogurt, and milk+yogurt+cheese intakes with quantitative computed tomography (QCT) measures of bone were examined, and we determined if associations were modified by serum vitamin D (25‐OH D, tertiles) or age (<50 versus ≥50 years). Participants were 1522 men and 1104 women (aged 32 to 81 years, mean 50 years [men]; 55 years [women]) from the Framingham Heart Study with measures of dairy food intake (servings/wk) from a food‐frequency questionnaire, volumetric BMD (vBMD, integral and trabecular, g/cm3), cross‐sectional area (CSA, cm2), and estimated vertebral compressive strength (VCS, N) and 25‐OH D (radioimmunoassay). Sex‐specific multivariable linear regression was used to calculate the association of dairy food intake (energy adjusted) with each QCT measure, adjusting for covariates. Mean milk intake ±SD was 6 ± 7 servings/week in both men and women. In men, higher intake of milk, milk+yogurt, and milk+yogurt+cheese was associated with higher integral (p = 0.001 to 0.006) and trabecular vBMD (p = 0.006 to 0.057) and VCS (p = 0.001 to 0.010). Further, a higher cheese intake was related with higher CSA (p = 0.049). In women, no significant results were observed for the dairy foods, except for a positive association of cream intake with CSA (p = 0.016). The associations appeared to be stronger in older men. Across 25‐OH D tertiles, dairy was positively associated with bone health. In summary, men with higher intakes of milk, milk+yogurt, and milk+yogurt+cheese had higher trabecular and integral vBMD and VCS but not CSA. Dairy intake seems to be most beneficial for older men, and dairy continued to have positive associations among all 25‐OH D levels. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article looks at the important advances in the clinical research of bone diseases and disorders of mineral metabolism by focusing on the developments in the treatment of osteoporosis along with reducing the risk of fractures.

ABSTRACT During lactation, mammals resorb mineral from the maternal skeleton to provide calcium to milk. Rodents lose 25% to 35% of skeletal ash weight, ash calcium content, and bone mineral content as measured by dual-energy X-ray absorptiometry (DXA), and have compromised material properties of bone as assessed by crushing vertebrae and 3-point bend tests of femora or tibias. The strength, stiffness, and toughness of vertebrae, femora, and tibias are reduced by as much as 60%. The effects of lactation are not uniform throughout the skeleton, but instead resorption is much more marked in the trabecular-rich spine than in the appendicular skeleton or whole body. Women who breastfeed exclusively lose an average of 210 mg calcium in milk each day, whereas nursing of twins or triplets can double and triple the output of calcium. Clinical data are also consistent with skeletal calcium being released during lactation to provide much of the calcium needed for milk production. Lumbar spine bone mineral density (BMD), as assessed by DXA, declines by a mean of 5% to 10% among numerous studies during 3 to 6 months of exclusive lactation, whereas largely cortical sites (hip, forearm, whole body) show half that loss or no significant changes. Micro-CT of rodents and high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of women confirm that lactation causes microarchitectural deterioration of bone. These skeletal losses occur through two pathways: upregulated osteoclast-mediated bone resorption and osteocytic osteolysis, in which osteocytes remove mineral from their lacunae and pericanalicular spaces. After weaning, the skeleton is fully restored to its prior mineral content and strength in both animal models and humans, despite persistent microarchitectural changes observed in high-resolution imaging. Osteoblasts upregulate to lay down new osteoid, while osteocytes remineralize their surroundings. The factors that stimulate this post-weaning skeletal recovery remain unclear. In most studies, a history of lactation does not increase the risk, but may protect against, low BMD and fragility fractures. © 2017 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this longitudinal study was to investigate long-term associations between low dietary calcium intake and fracture risk in older adults with plant-based diet. Data of self-reported first fracture events of any type from 6210 Chinese men and women, aged 50 years or older and free from fracture at baseline, in a subcohort based on the China Health and Nutrition Survey (CHNS), were analyzed. Diet was repeatedly assessed by a combination of three consecutive 24-hour individual dietary recalls and a weighing and measuring of household food inventory in each round. The older men and women habitually ingested mean (SD) of 415 (147) mg/d and 373 (140) mg/d of calcium from plant-based diet, respectively. During a median follow-up of 7.0 years, 127 men (4.34%) and 232 women (7.06%) experienced first fracture events. The crude rates were 4.88, 2.55, and 6.83 per 1000 person-years at risk for men, and 6.72, 7.10, and 11.0 per 1000 person-years at risk for women in the lowest, third, and highest quintile of dietary calcium intake. In nonlinear regressions, an increased risk of fracture was associated with dietary calcium intake more than 778 mg/d (multivariable adjusted hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.00-4.41) or lower than 275 mg/d (1.74, 95% CI 1.00-3.01) for men and more than 651 mg/d for women (1.54, 95% CI 1.00-2.38). A nonsignificant trend of increase in fracture risk was found below 248 mg/d (1.00, 95% CI 0.67-1.50) in women using restricted cubic spline Cox regression. A relatively low fracture risk is observed in men with dietary calcium intakes of 275 to 780 mg/d and in women with intakes of 250 to 650 mg/d, and higher intakes may have no further benefit for fracture prevention. The patterns of dietary calcium with fracture risk are U-shaped in men and possibly in women. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Calcium supplementation is indicated for the treatment of nutritional rickets. Our aim was to determine the optimal dose of calcium for treatment of children with rickets. Sixty-five Nigerian children with radiographically confirmed rickets were randomized to daily supplemental calcium intake of 500 mg ( n = 21), 1000 mg ( n = 23), or 2000 mg ( n = 21). Venous blood, radiographs, and forearm areal bone density (aBMD) were obtained at baseline and at 8, 16, and 24 weeks after enrollment. The primary outcome was radiographic healing, using a 10-point radiographic severity score. The radiographic severity scores improved in all three groups, but the rate of radiographic healing (points per month) was significantly more rapid in the 1000-mg (-0.29; 95% confidence interval [CI] -0.13 to -0.45) and 2000-mg (-0.36; 95% CI -0.19 to -0.53) supplementation groups relative to the 500-mg group. The 2000-mg group did not heal more rapidly than the 1000-mg group. Of those who completed treatment for 24 weeks, 12 (67%), 20 (87%), and 14 (67%) in the 2000-mg, 1000-mg, and 500-mg groups, respectively, had achieved a radiographic score of 1.5 or less ( p = 0.21). Serum alkaline phosphatase decreased and calcium increased similarly in all groups. Forearm diaphyseal aBMD improved significantly more rapidly in the 2000-mg group than in the 500-mg and 1000-mg groups ( p < 0.001). Daily calcium intakes of 1000 mg or 2000 mg produced more rapid radiographic healing of rickets than 500 mg, but 2000 mg did not have greater benefit than 1000 mg. Some children require longer than 24 weeks for complete healing of nutritional rickets. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Thiazide diuretic (TZ) use is associated with higher bone mineral density, whereas loop diuretic (LD) use is associated with lower bone density and incident fracture. Dihydropyridine-sensitive calcium channels are expressed on parathyroid cells and may play a role in parathyroid hormone (PTH) regulation. The potential for diuretics and calcium-channel blockers (CCBs) to modulate PTH and calcium homeostasis may represent a mechanism by which they influence skeletal outcomes. We hypothesized that the use of LD and dihydropyridine CCBs is associated with higher PTH, and TZ use is associated with lower PTH. We conducted cross-sectional analyses of participants treated for hypertension in the Multi-Ethnic Study of Atherosclerosis who did not have primary hyperparathyroidism or chronic kidney disease ( n = 1888). We used adjusted regression models to evaluate the independent association between TZ, LD, and CCB medication classes and PTH. TZ use was associated with lower PTH when compared with non-TZ use (44.4 versus 46.9 pg/mL, p = 0.02), whereas the use of LD and CCBs was associated with higher PTH when compared with non-users of each medication class (LD: 60.7 versus 45.5 pg/mL, p < 0.0001; CCB: 49.5 versus. 44.4 pg/mL, p < 0.0001). Adjusted regression models confirmed independent associations between TZ use and lower PTH (β = -3.2 pg/mL, p = 0.0007), and LD or CCB use and higher PTH (LD: β = +12.0 pg/mL, p < 0.0001; CCB: +3.7 pg/mL, p < 0.0001). Among CCB users, the use of dihydropyridines was independently associated with higher PTH (β = +5.0 pg/mL, p < 0.0001), whereas non-dihydropyridine use was not (β = +0.58 pg/mL, p = 0.68). We conclude that in a large community-based cohort with normal kidney function, TZ use is associated with lower PTH, whereas LD and dihydropyridine CCB use is associated with higher PTH. These associations may provide a mechanistic explanation linking use of these medications to the development of skeletal outcomes. © 2016 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Although a higher protein intake, particularly from vegetable sources, has been shown to be associated with higher bone mineral density (BMD) the relative impact of specific amino acids on BMD and risk of osteoporosis remains to be determined. Mechanistic research suggests that a number of specific amino acids, including five nonessential amino acids-alanine, arginine, glutamic acid, glycine, and proline-may play a role in bone health, principally through improved production of insulin and insulin-like growth factor 1 and the synthesis of collagen and muscle protein. However to date, no previous studies have examined the associations between habitual intake of amino acids and direct measures of BMD and prevalence of osteoporosis or osteopenia, and no studies have examined this relationship in discordant identical twin-pairs. In these analyses of female monozygotic twin-pairs discordant for amino acid intake ( n = 135), twins with higher intakes of alanine and glycine had significantly higher BMD at the spine than their co-twins with within-pair differences in spine-BMD of 0.012 g/cm2 (SE 0.01; p = 0.039) and 0.014 g/cm2 (SE 0.01; p = 0.026), respectively. Furthermore, in cross-sectional multivariable analyses of 3160 females aged 18 to 79 years, a higher intake of total protein was significantly associated with higher DXA-measured BMD at the spine (quartile Q4 to quartile Q1: 0.017 g/cm2, SE 0.01, p = 0.035) and forearm (Q4 to Q1: 0.010 g/cm2, SE 0.003, p = 0.002). Intake of six amino acids (alanine, arginine, glutamic acid, leucine, lysine, and proline) were associated with higher BMD at the spine and forearm with the strongest association observed for leucine (Q4 to Q1: 0.024 g/cm2, SE 0.01, p = 0.007). When intakes were stratified by protein source, vegetable or animal, prevalence of osteoporosis or osteopenia was 13% to 19% lower comparing extreme quartiles of vegetable intake for five amino acids (not glutamic acid or proline). These data provide evidence to suggest that intake of protein and several amino acids, including alanine and glycine, may be beneficial for bone health, independent of genetic background. © 2015 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO3) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double-blind, randomized, placebo-controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO3 daily for 3 months; 233 completed the study. The primary outcomes were changes in 24-hour urinary N-telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24-hour urinary calcium excretion, serum amino-terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low-dose and high-dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low-dose group ( p = 0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low-dose group ( p = 0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO3 groups versus placebo ( p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO3 on urinary N excretion or on the physical strength and function measures. KHCO3 has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long-term trials to assess the effect of alkali on bone mass and fracture risk are needed. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this population-based, prospective cohort study was to investigate long-term associations between dietary calcium intake and fractures, non-fatal cardiovascular disease (CVD), and death from all causes. Participants were from the Melbourne Collaborative Cohort Study, which was established in 1990 to 1994. A total of 41,514 men and women (∼99% aged 40 to 69 years at baseline) were followed up for a mean (SD) of 12 (1.5) years. Primary outcome measures were time to death from all causes ( n = 2855), CVD-related deaths ( n = 557), cerebrovascular disease-related deaths ( n = 139), incident non-fatal CVD ( n = 1827), incident stroke events ( n = 537), and incident fractures ( n = 788). A total of 12,097 participants (aged ≥50 years) were eligible for fracture analysis and 34,468 for non-fatal CVD and mortality analyses. Mortality was ascertained by record linkage to registries. Fractures and CVD were ascertained from interview ∼13 years after baseline. Quartiles of baseline energy-adjusted calcium intake from food were estimated using a food-frequency questionnaire. Hazard ratios (HR) and odds ratios (OR) were calculated for quartiles of dietary calcium intake. Highest and lowest quartiles of energy-adjusted dietary calcium intakes represented unadjusted means (SD) of 1348 (316) mg/d and 473 (91) mg/d, respectively. Overall, there were 788 (10.3%) incident fractures, 1827 (9.0%) incident CVD, and 2855 people (8.6%) died. Comparing the highest with the lowest quartile of calcium intake, for all-cause mortality, the HR was 0.86 (95% confidence interval [CI] 0.76-0.98, ptrend = 0.01); for non-fatal CVD and stroke, the OR was 0.84 (95% CI 0.70-0.99, ptrend = 0.04) and 0.69 (95% CI 0.51-0.93, ptrend = 0.02), respectively; and the OR for fracture was 0.70 (95% CI 0.54-0.92, ptrend = 0.004). In summary, for older men and women, calcium intakes of up to 1348 (316) mg/d from food were associated with decreased risks for fracture, non-fatal CVD, stroke, and all-cause mortality. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article discusses about the importance of Vitamin D for the maintenance of bone mass and calcium homeostasis during pregnancy and lactation.

ABSTRACT We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study ( n = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single-nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between an SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex•SNP interaction, revealing a significant association only in females (b = -0.32, p = 1.8 × 10-6). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, p = 0.001) and femoral neck aBMD (b = 0.27, p = 3.0 × 10-5). In contrast, the sex•SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, p = 4.4 × 10-4) and distal radius aBMD (b = 0.27, p = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, p = 0.003). In total, significant sex•SNP interactions were found at 15 loci; pubertal stage•SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation. © 2015 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Dietary guidelines recommend a daily intake of 5 servings of fruits and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose-response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n = 75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45 to 83 years). Intake of fruits and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998 to 2010). The mean follow-up time was 14.2 years. One-third of the participants reported an intake of fruits and vegetables of >5 servings/day, one-third reported >3 to ≤5 servings/day, 28% reported >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person-years we observed 3644 hip fractures (2266 or 62% in women). The dose-response association was found to be strongly nonlinear ( p < 0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR) was 1.88 (95% CI, 1.53 to 2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 versus 5 servings/day was 1.35 (95% CI, 1.21 to 1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 versus 5 servings/day was 0.96; 95% CI, 0.90 to 1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose-response association between fruit and vegetable intake and hip fracture such that an intake below the recommended five servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk. © 2014 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article offers information on nomenclature, Symbols and Units related to Bone Histomorphometry as per report by American Society for Bone and Mineral Research Histomorphometry Nomenclature Committee. Terminology related to nomenclature is mentioned with various terms including Standard Format, Area measurements and Structural indices.

Young female gymnasts have greater bone strength compared to controls; although possibly due to selection into gymnastics, it is thought that their loading activity during growth increases their bone mass, influencing both bone geometry and architecture. If such bone mass and geometric adaptations are maintained, this may potentially decrease the risk of osteoporosis and risk of fracture later in life. However, there is limited evidence of the persisting benefit of gymnastic exercise during growth on adult bone geometric parameters. Therefore, the purpose of this study was to determine whether adult bone geometry, volumetric density, and estimated strength were greater in retired gymnasts compared to controls, 10 years after retirement from the sport. Bone geometric and densitometric parameters, measured by peripheral quantitative computed tomography (pQCT) at the radius and tibia, were compared between 25 retired female gymnasts and 22 controls, age range 22 to 30 years, by multivariate analysis of covariance (covariates: age, height, and muscle cross-sectional area). Retired gymnasts had significantly greater adjusted total and trabecular area (16%), total and trabecular bone mineral content (BMC) (18% and 22%, respectively), and estimated strength (21%) at the distal radius ( p < 0.05) than controls. Adjusted total and cortical area and BMC, medullary area, and estimated strength were also significantly greater (13% to 46%) in retired gymnasts at the 30% and 65% radial shaft sites ( p < 0.05). At the distal tibia, retired gymnasts had 12% to 13% greater total and trabecular BMC and volumetric bone mineral density as well as 21% greater estimated strength; total and cortical BMC and estimated strength were also greater at the tibial shaft (8%, 11%, and 10%, respectively) ( p < 0.05). Former female gymnasts have significantly better geometric and densitometric properties, as well as estimated strength, at the radius and tibia 10 years after retirement from gymnastics compared to females who did not participate in gymnastics in childhood and adolescence. © 2012 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an apical membrane calcium (Ca) channel in the small intestine proposed to be essential for vitamin D-regulated intestinal Ca absorption. Recent studies have challenged the proposed role for TRPV6 in Ca absorption. We directly tested intestinal TRPV6 function in Ca and bone metabolism in wild-type (WT) and vitamin D receptor knockout (VDRKO) mice. TRPV6 transgenic mice (TG) were made with intestinal epithelium-specific expression of a 3X Flag-tagged human TRPV6 protein. TG and VDRKO mice were crossed to make TG-VDRKO mice. Ca and bone metabolism was examined in WT, TG, VDRKO, and TG-VDRKO mice. TG mice developed hypercalcemia and soft tissue calcification on a chow diet. In TG mice fed a 0.25% Ca diet, Ca absorption was more than three-fold higher and femur bone mineral density (BMD) was 26% higher than WT. Renal 1α hydroxylase (CYP27B1) mRNA and intestinal expression of the natural mouse TRPV6 gene were reduced to <10% of WT but small intestine calbindin-D9k expression was elevated >15 times in TG mice. TG-VDRKO mice had high Ca absorption that prevented the low serum Ca, high renal CYP27B1 mRNA, low BMD, and abnormal bone microarchitecture seen in VDRKO mice. In addition, small intestinal calbindin D9K mRNA and protein levels were elevated in TG-VDRKO. Transgenic TRPV6 expression in intestine is sufficient to increase Ca absorption and bone density, even in VDRKO mice. VDR-independent upregulation of intestinal calbindin D9k in TG-VDRKO suggests this protein may buffer intracellular Ca during Ca absorption. © 2012 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is associated with rapid and sustained bone loss and increase risk of fracture. Disuse is the primary cause for bone loss, although neural and hormonal changes may also contribute via different mechanisms. Bisphosphonates are used widely to treat osteoporosis in adults and are used increasingly for primary and secondary osteoporosis in children. Current data are insufficient to recommend routine use of bisphosphonates for fracture prevention in adult patients post-SCI and there are no available data in pediatric SCI. We report a 12-year-old boy with non-traumatic SCI who was treated with six monthly zoledronic acid (0.05 mg/kg/dose) for 18 months. The patient (AA) was diagnosed with transverse myelitis at 8.1 years of age, resulting in ventilator-dependent incomplete C3 tetraplegia. Following a fragility fracture to the surgical neck of the right humerus at 9.5 years of age, he was started on zoledronic acid. Bone turnover decreased and bone densitometry data (dual-energy X-ray absorptiometry [DXA] and peripheral quantitative computed tomography [pQCT]) showed improvement in metaphyseal and diaphyseal bone mineral content (BMC), volumetric bone mineral density (vBMD), and size, after 18 months of treatment. In the growing skeleton post-SCI, zoledronic acid potentially increases vertebral and long-bone strength by preserving trabecular bone (increased BMC and vBMD) and increasing cortical vBMD and cross-sectional area (CSA). © 2012 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the sex- and maturity-related differences in bone microstructure and estimated bone strength at the distal radius and distal tibia in children and adolescents. We used high-resolution pQCT to measure standard morphological parameters in addition to cortical porosity (Ct.Po) and estimated bone strength by finite element analysis. Participants ranged in age from 9 to 22 years ( n = 212 girls and n = 186 boys) who were scanned annually for either one (11%) or two (89%) years at the radius and for one (15%), two (39%), or three (46%) years at the tibia. Participants were grouped by the method of Tanner into prepubertal, early pubertal, peripubertal, and postpubertal groups. At the radius, peri- and postpubertal girls had higher cortical density (Ct.BMD; 9.4% and 7.4%, respectively) and lower Ct.Po (-118% and-56%, respectively) compared with peri- and postpubertal boys (all p < 0.001). Peri- and postpubertal boys had higher trabecular bone volume ratios ( p < 0.001) and larger cortical cross-sectional areas ( p < 0.05, p < 0.001) when compared with girls. Based upon the load-to-strength ratio (failure load/estimated fall force), boys had lower risk of fracture than girls at every stage except during early puberty. Trends at the tibia were similar to the radius with differences between boys and girls in Ct.Po ( p < 0.01) and failure load ( p < 0.01) at early puberty. Across pubertal groups, within sex, the most mature girls and boys had higher Ct.BMD and lower Ct.Po than their less mature peers (prepuberty) at both the radius and tibia. Girls in early, peri-, and postpubertal groups and boys in peri- and postpubertal groups had higher estimates of bone strength compared with their same-sex prepubertal peers ( p < 0.001). These results provide insight into the sex- and maturity-related differences in bone microstructure and estimated bone strength. © 2012 American Society for Bone and Mineral Research [ABSTRACT FROM AUTHOR]

Prolonged bed rest is used to simulate the effects of spaceflight and causes disuse-related loss of bone. While bone density changes during bed rest have been described, there are no data on changes in bone microstructure. Twenty-four healthy women aged 25 to 40 years participated in 60 days of strict 6-degree head-down tilt bed rest (WISE 2005). Subjects were assigned to either a control group (CON, n = 8), which performed no countermeasures; an exercise group (EXE, n = 8), which undertook a combination of resistive and endurance training; or a nutrition group (NUT, n = 8), which received a high-protein diet. Density and structural parameters of the distal tibia and radius were measured at baseline, during, and up to 1 year after bed rest by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bed rest was associated with reductions in all distal tibial density parameters ( p < 0.001), whereas only distal radius trabecular density decreased. Trabecular separation increased at both the distal tibia and distal radius ( p < 0.001), but these effects were first significant after bed rest. Reduction in trabecular number was similar in magnitude at the distal radius ( p = 0.021) and distal tibia ( p < 0.001). Cortical thickness decreased at the distal tibia only ( p < 0.001). There were no significant effects on bone structure or density of the countermeasures ( p ≥ 0.057). As measured with HR-pQCT, it is concluded that deterioration in bone microstructure and density occur in women during and after prolonged bed rest. The exercise and nutrition countermeasures were ineffective in preventing these changes. © 2011 American Society for Bone and Mineral Research [ABSTRACT FROM AUTHOR]