Total and free vitamin D metabolites in patients with primary hyperparathyroidism.

PURPOSE: To evaluate total and free vitamin D metabolites and hormone-to-prohormone [1,25(OH)2D/25(OH)D] "activation ratio" in PHPT patients with low or insufficient vitamin D status. METHODS: Thirty female patients with primary hyperparathyroidism (PHPT) and 30 age and body mass index (BMI) matched healthy controls were enrolled. Serum levels of calcium, intact parathyroid hormone (iPTH), vitamin D binding protein (DBP), albumin, total 25(OH)D and 1,25(OH)2D were measured. The activation ratio of vitamin D was calculated as total 1,25(OH)2D/25(OH)D. Calculated serum-free 25(OH)D and 1,25(OH)2D levels were also reported. RESULTS: Compared to the control subject, patients with PHPT had a lower total 25(OH)D and DBP levels (p < 0.001). The serum concentration of free 25(OH)D and total 1,25(OH)2D were similar between the two groups; but free 1,25(OH)2D levels were about 26% higher in the PHPT patients compared to controls (p < 0.001). PHPT patients had a significantly higher activation ratio (p < 0.01), although their total 25(OH)D were lower than controls. The free (but not total) 1,25(OH)2D level was inversely correlated with DBP (p < 0.01). Both free 1,25(OH)2D levels and activation ratio were positively correlated with iPTH and calcium levels (p < 0.01). The activation ratio was highly correlated with levels of total vitamin D stores and free vitamin D metabolites (p < 0.001). CONCLUSION: Patients with PHPT had significantly higher free 1,25(OH)2D levels and activation ratio compared to control subjects. We suggest that levels of free vitamin D metabolites and vitamin D activation ratio may provide additional values for the diagnosis and therapeutic choices in these patient populations with compromised vitamin D status.

Decreased fasting serum glucogenic amino acids with a higher compared to normal protein diet during energy restriction in women: a randomized controlled trial.

Dietary protein alters circulating amino acid (AAs) levels and higher protein intake (HP) is one means of losing weight. We examined 34 overweight and obese women (57 ± 4 years) during 6 months of energy restriction (7.3 ± 3.8% weight loss) divided into groups consuming either normal protein (NP; 18.6 energy% protein) or HP (24.3 energy% protein). There was a reduction in fasting serum glucogenic AAs (p = 0.015) that also associated with greater weight loss (p < 0.05) in the HP group, but not in the NP group. These findings have implications for nutrient prioritization during energy restriction.

Reduced postprandial bone resorption and greater rise in GLP-1 in overweight and obese individuals after an α-glucosidase inhibitor: a double-blinded randomized crossover trial.

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. INTRODUCTION: Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. METHODS: In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21-59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. RESULTS: Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). CONCLUSION: This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.

Can Dietary Fatty Acids Affect the COVID-19 Infection Outcome in Vulnerable Populations?

There is high mortality in coronavirus disease 2019 (COVID-19)-infected individuals with chronic inflammatory diseases, like obesity, diabetes, and hypertension. A cytokine storm in some patients after infection contributes to this mortality. In addition to lungs, the intestine is targeted during COVID-19 infection. The intestinal membrane serves as a barrier to prevent leakage of microorganisms and their products into the bloodstream; however, dietary fats can affect the gut microbiome and may increase intestinal permeability. In obese or diabetic individuals, there is an increase in the abundance of either Gram-negative bacteria in the gut or their product, endotoxin, in systemic circulation. We speculate that when the COVID-19 infection localizes in the intestine and when the permeability properties of the intestinal membrane are compromised, an inflammatory response is generated when proinflammatory endotoxin, produced by resident Gram-negative bacteria, leaks into the systemic circulation. This review discusses conditions contributing to inflammation that are triggered by microbially derived factors from the gut.

Circulating zearalenone and its metabolites differ in women due to body mass index and food intake.

The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52 ±â€¯9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (p = 0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480 g/d) compared those with lowest (<115 g/d) meat consumption had higher conjugated serum ZEA metabolite concentrations (p < 0.05). Intakes of other food groups (i.e., dairy, cereal, etc.) were not associated with ZEA metabolites. These findings indicate that ZEA and its metabolites are detectable in nearly all women and concentrations are associated with greater meat intake, and influenced by body mass index. Determining how the food supply influences human concentrations of ZEA metabolites is warranted, as well as determining vulnerable populations.

The influence of dietary fat and intestinal pH on calcium bioaccessibility: an in vitro study.

In vivo studies measuring true fractional calcium (Ca) absorption have shown that dietary fat is a significant predictor of absorption and is influenced by luminal pH levels. However, whether changes in Ca bioaccessibility (CaB) can explain the effects on absorption has not been examined. In the current study, we examined two high fat diets enriched in either monounsaturated fatty acids or saturated fatty acids (SFA), and a low-fat diet (LFD), each with 50 mg Ca, and measured CaB at different intestinal regions during normal acidic or higher (pH = 7) gastrointestinal conditions using an in vitro gastrointestinal model. During normal pH conditions in the jejunum, there was an interaction between diet and time for CaB (P < 0.02), and CaB during the SFA diet was higher than LFD (P = 0.05). CaB was reduced by 90 ± 3% during higher compared with normal pH under all dietary conditions (P < 0.001). These findings indicate that fat intake, especially SFA enriched, is associated with a greater CaB in the jejunum, and may explain the higher Ca absorption in previous studies. In addition, the marked reduction in CaB under higher pH conditions could have implications in persons taking medications to reduce gastric acid.

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry. INTRODUCTION: Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance. METHODS: This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined. RESULTS: Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m2, serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05). CONCLUSION: The decline in Ct thickness was prevented with higher vitamin D3 supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption: BsmI predicts a greater decrease during energy restriction.

Low calcium absorption is associated with low bone mass and fracture. In this study, we use gold standard methods of fractional calcium absorption (FCA) to determine whether polymorphisms of intestinal receptors, vitamin D receptor (VDR) and estrogen receptor α (ESR1), influence the response to energy restriction. Fractional calcium absorption was measured using dual stable isotopes ((42)Ca and (43)Ca) in women given adequate calcium and vitamin D and examined at baseline and after 6 weeks of energy restriction or no intervention. After genotyping, the relationship between VDR and ESR1 genotypes/haplotypes and FCA response was assessed using several genetic models. One-hundred and sixty-eight women (53 ± 11 years of age) were included in this analysis. The ESR1 polymorphisms, PvuII and XbaI and VDR polymorphisms (TaqI, ApaI) did not significantly influence FCA. The BB genotype of the VDR polymorphism, BsmI, was associated with a greater decrease in FCA than the Bb/bb genotype. Multiple linear regression showed that the BsmI polymorphism or the VDR haplotype, BAt, in addition to changes in weight and vitamin D intake explained ~16% of the variation in changes in FCA. In conclusion, the reduction in calcium absorption due to energy restriction is greatest for those with the BB genotype. Previous candidate gene studies show that VDR polymorphisms are associated with higher risk for osteoporosis, and the current study supports the notion that the BsmI polymorphism in intestinal VDR may be contributing to alterations in bone health.

Vitamin D supplementation during short-term caloric restriction in healthy overweight/obese older women: Effect on glycemic indices and serum osteocalcin levels.

The effect of vitamin D supplementation and caloric restriction (CR) on glycemic indices and osteocalcin (OC) is not clear. In this randomized controlled double blind trial, we examined whether vitamin D3 supplementation at 2500 IU/d (D) or placebo has differential effects on markers of insulin sensitivity and bone turnover in overweight/obese postmenopausal women during 6 weeks of caloric restriction (weight loss; WL, n = 39) compared to weight maintenance (WM, n = 37). Seventy-six women (57 ± 6 years) completed this study and the WL groups lost 4 ± 1% of body weight. Baseline serum 25-hydroxyvitamin D (25OHD) was 24.8 ± 5.6 ng/mL at baseline; the rise was greatest in WL-D group (p < 0.05). There was an interaction between vitamin D intake and weight on serum OC, insulin, glucose and markers of insulin sensitivity (p < 0.05). The change in OC was explained by changes in serum 25OHD and insulin (model R(2) = 25.6%). Overall, vitamin D supplementation and CR influence serum osteocalcin levels and modestly favor improvements in insulin sensitivity.

The independent and combined effects of intensive weight loss and exercise training on bone mineral density in overweight and obese older adults with osteoarthritis.

OBJECTIVE: To determine the effects of dietary-induced weight loss (D) and weight loss plus exercise (D + E) compared to exercise alone (E) on bone mineral density (BMD) in older adults with knee osteoarthritis (OA). DESIGN: Data come from 284 older (66.0 ± 6.2 years), overweight/obese (body mass index (BMI) 33.4 ± 3.7 kg/m2), adults with knee OA enrolled in the Intensive Diet and Exercise for Arthritis (IDEA) study. Participants were randomized to 18 months of walking and strength training (E; n = 95), dietary-induced weight loss targeting 10% of baseline weight (D; n = 88) or a combination of the two (D + E; n = 101). Body weight and composition (DXA), regional BMD, were obtained at baseline and 18 months. RESULTS: E, D, and D + E groups lost 1.3 ± 4.5 kg, 9.1 ± 8.6 kg and 10.4 ± 8.0 kg, respectively (P < 0.01). Significant treatment effects were observed for BMD in both hip and femoral neck regions, with the D and D + E groups showing similar relative losses compared to E (both P < 0.01). Despite reduced BMD, fewer overall participants had T-scores indicative of osteoporosis after intervention (9 at 18 months vs 10 at baseline). Within the D and D + E groups, changes in hip and femoral neck, but not spine, BMD correlated positively with changes in body weight (r = 0.21 and 0.54 respectively, both P ≤ 0.01). CONCLUSIONS: Weight loss via an intensive dietary intervention, with or without exercise, results in bone loss at the hip and femoral neck in overweight and obese, older adults with OA. Although the exercise intervention did not attenuate weight loss-associated reductions in BMD, classification of osteoporosis and osteopenia remained unchanged. CLINICAL TRIAL REGISTRATION NUMBER: NCT00381290.

Hormonal and dietary influences on true fractional calcium absorption in women: role of obesity.

UNLABELLED: The goal in this study was to examine the hormonal and dietary predictors of true fractional Ca absorption (TFCA) in adult women and to determine whether TFCA differs due to body weight. Results showed that TFCA is higher in obese individuals and dietary fat, estradiol, and 1,25-dihydroxy vitamin D are the most significant positive predictors of TFCA in adult women. INTRODUCTION: Calcium absorption is an important determinant of calcium balance and is influenced by several factors. Previous studies have identified that age, intake of protein, fat and fiber, and hormones such as 1, 25-dihyroxyvitamin D (1,25(OH)(2)D(3)) influence absorption. The determinants of TFCA using the double isotope method, the gold standard estimate of absorption, have not been examined previously in adult women nor has the role of obesity been addressed. METHODS: In this study, we examined the hormonal and dietary predictors of TFCA in adult women with a wide range of age, body weights, and nutrient intake. TFCA was measured using dual stable isotope ((42)Ca and (43)Ca) technique. Serum was analyzed for bone-regulating hormones, and dietary information was obtained through food records. The independent dietary factors and hormonal predictors (25-hydroxyvitamin D, 1,25(OH)(2)D(3), parathyroid hormone, and estradiol) of TFCA were analyzed using multiple regression analysis. RESULTS: Two hundred twenty-nine women aged 54 ± 11 years old (24-75 years) and with BMI of 31 ± 7.0 kg/m(2) were eligible and were categorized into tertiles of body mass index (BMI) into leaner, overweight, and obese. In the entire group of women, total fat intake, estradiol, and 1,25(OH)(2)D(3) are significant positive predictors (p < 0.05). As expected, age is a significant negative predictor of TFCA (R (2) = 26%). TFCA is higher in obese women compared to non-obese women (p < 0.05). CONCLUSION: Together, these data show that dietary fat is the most significant positive predictor of TFCA which may have implications for dietary intake for non-obese individuals who are more likely to have lower and potentially compromised Ca absorption.

The high serum monocyte chemoattractant protein-1 in obesity is influenced by high parathyroid hormone and not adiposity.

CONTEXT: Chronic high levels of PTH may be associated with up-regulation of proteases and cytokines. Monocyte chemoattractant protein-1 (MCP-1) is an inflammatory cytokine, produced predominantly by macrophages and endothelial cells, and is expressed in adipose tissue. More recently it has been shown that PTH administration increases MCP-1 expression in osteoblasts. OBJECTIVES: Because both PTH and MCP-1 levels are higher in obesity, the goal was to determine whether the high MCP-1 occurs only in the presence of high serum PTH and is independent of adiposity and examine its relationship with bone mineral density (BMD) and turnover. DESIGN, SETTING, AND PARTICIPANTS: In this case-control clinical design, 111 eligible women were categorized into four groups: leaner women [body mass index (BMI) 23 ± 2 kg/m(2)] with normal or higher PTH and obese (BMI 44 ± 7 kg/m(2)) with normal or higher PTH. RESULTS: Serum MCP-1 levels were higher (P < 0.01) in the high (PTH = 74.9 ± 27.0 pg/ml, MCP-1 = 421.5 ± 157.0 pg/ml) compared with normal PTH (PTH = 32.5 ± 10.4 pg/ml, MCP-1 = 322.5 ± 97.8 pg/ml) group, independent of BMI. C-reactive protein and adiponectin were influenced only by BMI and not PTH. MCP-1 was positively associated with osteocalcin and propeptide of type 1 collagen in the leaner (r > 0.3, P < 0.05) but not the obese women and was not associated with BMD in either group. CONCLUSIONS: Together these data suggest that MCP-1 is higher only in the presence of increased PTH and that adiposity alone cannot explain the higher MCP-1 levels in obesity.

Obesity alters cortical and trabecular bone density and geometry in women.

UNLABELLED: The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone using quantitative computed tomography. A higher body mass index (BMI) was positively associated with trabecular and cortical bone parameters, and serum parathyroid hormone, and negatively associated with cortical volumetric bone mineral density (vBMD) and serum 25-hydroxy-vitamin D. When BMI is greater than 35 kg/m(2), adiposity affects vBMD and may explain the higher fracture risk in this population without low BMD. INTRODUCTION: The influence of adult obesity on the trabecular and cortical bone, geometry, and strength has not been fully addressed. The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone mass and geometry, over a wide range of body weights. METHODS: We examined 211 women (25-71 years; BMI 18-57 kg/m(2)) who were classified into three categories of BMI (kg/m(2)) including normal-weight (BMI<25), overweight and obese-class I (BMI 25-35) and obese-class II-III (BMI>35), and also by menopausal status. Volumetric bone mineral density (mg/cm(3)), trabecular, and cortical components as well as geometric characteristics at the 4%, 38%, and 66% from the distal tibia were measured by peripheral quantitative computed tomography, and serum was analyzed for parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD). RESULTS: Higher BMI was associated with greater values of trabecular bone and cortical BMC and area and PTH (r>0.39, p<0.001), but lower cortical vBMD and 25OHD (r>-0.27, p<0.001). When controlling for lower leg muscle area, fat area was inversely associated with cortical vBMD (r=-0.16, p<0.05). Premenopausal obese women with both higher BMI and PTH had lower cortical vBMD (r<-0.40, p<0.001). While age is a predictor for most bone variables, fat mass explains more variance for vBMD, and lean mass and 25OHD explain greater variance in geometric and strength indices (p<0.05). CONCLUSIONS: Severe obesity (BMI>35) increases trabecular vBMD and in the presence of a higher PTH is associated with a lower cortical vBMD without compromising bone geometry and strength. Whether or not a lower cortical vBMD in obesity influences fracture risk over time needs to be further explored.

Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency.

Osteopontin null-mice were previously shown to have bones containing more mineral and larger mineral crystals. These bones were independently seen to be resistant to ovariectomy-induced remodeling. To separate the physicochemical effects of osteopontin, which is an in vitro inhibitor of mineral crystal formation and growth, from effects of osteopontin on in vivo bone remodeling, this study examined mature (5-month-old) osteopontin-null (Opn-/-) and wildtype (WT) mice given a calcium-deficient diet. Biochemical parameters were measured during 4 weeks of Ca deficiency, followed by 1 week of refeeding adequate Ca. Ca deficiency caused a transiently greater rise in bone resorption in WT than Opn-/- mice (P = 0.01), whereas only the Opn-/- mice tended to increase Ca absorption (P = 0.08), yet both groups showed elevated levels of parathyroid hormone (PTH) (P < 0.001). The rise in markers of bone formation due to Ca deficiency was similar in both groups during Ca deficiency. Fourier transform infrared microspectroscopy assessed mineral properties at 20 microm spatial resolution in different anatomic regions of the bone. The Ca-deficient Opn-/- animals had slightly increased mineral content as compared to the WT, and there was a significant increase in the mineral content of older (endosteal) bone, implying that osteoclast recruitment was impaired. Crystallinity in the Ca-deficient Opn-/- bones was increased relative to the Ca-deficient WT at all sites except adjacent to the periosteum (younger mineral). These data suggest that osteopontin has both a physicochemical effect (inhibiting crystal growth and crystal proliferation) and a role in osteoclast recruitment, and in its absence, extraskeletal organs maintain calcium homeostasis.

Bone turnover and body weight relationships differ in normal-weight compared with heavier postmenopausal women.

Low body weight is associated with increased risk for fractures, whereas higher body weight has been shown to be protective against osteoporosis. This study evaluated whether body weight plays a role regulating bone turnover and mass in normal-weight (body mass index (BMI) <25 kg/m2), overweight (BMI 25-29.9 kg/m2) and obese (BMI> or =30 kg/m2) postmenopausal women who were either receiving hormone replacement therapy [HRT(+)] or not [HRT(-)] (total of six groups). Body weight, BMI, total body bone mineral content (TBBMC), and markers of bone formation (serum osteocalcin) and bone resorption (urinary pyridinoline (PYD) and deoxypyridinoline) were retrospectively analyzed in 210 postmenopausal women. The mean age was 67+/-6 years, with mean body weight of 70.8+/-14.2 kg, ranging from 45.0 to 115.5 kg. Body weight was positively correlated with TBBMC ( r=0.50, p<0.0001). There was a lower TBBMC and higher bone formation rate in normal-weight than obese HRT(-) women, but in women taking HRT there were no differences between BMI categories. In addition, in normal-weight HRT(-) women only, PYD and body weight showed a negative correlation (r=-0.39, p=0.01). Among normal-weight, but not overweight or obese subjects, we observed higher TBBMC and lower bone turnover in the HRT(+) compared with the HRT(-) group. Regression models explained 36% of the variance in TBBMC, mainly through body weight. Additional models could only explain 11-15% of the variance in bone turnover. Taken together, these data suggest that among normal-weight but not obese postmenopausal women, higher bone turnover is associated with lower bone mass, and that only normal-weight women show a different bone turnover profile with HRT treatment. Body weight should be considered an important factor in bone metabolism with relevant clinical implications.

Energy restriction reduces bone density and biomechanical properties in aged female rats.

Bone mineral density (BMD) is highly correlated with body weight, and weight loss is associated with reduced BMD. Whether such losses of BMD increase skeletal fragility is unclear. We examined the effect of 9 wk of energy restriction (ER) on bone density, mineral and matrix protein composition and biomechanical properties in mature (20 wk old, n = 12) and aged (48 wk old, n = 16) female rats. Energy-restricted rats were fed 40% less energy than controls that consumed food ad libitum. Bone content of mineral (ash and calcium content) and matrix proteins (hydroxyproline, pyridinium crosslinks and proteoglycans), serum hormones, site-specific bone density and biomechanical properties (peak load, peak torque, shear stiffness and bending stiffness) were measured at the conclusion of the study. In both age groups, ER reduced body weight by 15 +/- 10% (P < 0.001) and dramatically decreased femoral bone density by 32-35% (P < 0.01) compared with controls. Energy restriction resulted in a small reduction in tibia and humerus density, as well as biomechanical properties in the aged but not mature rats (P < 0.05). Reduced serum levels of insulin and estradiol due to ER in aged rats (P < 0.05) may play a role in altering bone quality. These data show that although weight loss due to ER is detrimental to some bone parameters in mature rats, only aged rats show consistent reductions in bone density and biomechanical properties.

Bone turnover and density in obese premenopausal women during moderate weight loss and calcium supplementation.

Bone turnover is increased during weight loss in postmenopausal women and can be suppressed with calcium supplementation. In this study, we assessed the influence of energy restriction with and without calcium supplementation (1 g/day) in premenopausal women. Thirty-eight obese premenopausal women (body mass index [BMI] of 35.0 +/- 3.9 kg/m2) completed a 6-month study of either moderate weight loss or weight maintenance. During weight loss, women were randomly assigned to either a calcium supplementation (n = 14) or placebo group (n = 14) and lost 7.5 +/- 2.5% of their body weight. The control group of women (n = 10) maintained their body weight. Total body and lumbar bone mineral density (LBMD) and content were measured by dual-energy X-ray absorptiometry (DXA) at baseline and after weight loss. Throughout the study, blood and urine samples were collected to measure bone turnover markers and hormones. During moderate energy restriction, dietary calcium intake decreased (p < 0.05) and the bone resorption marker deoxypyridinoline (DPD) increased slightly (p < or = 0.05) without evidence of bone loss. Calcium supplementation during weight loss tended to increase lumbar BMD by 1.7% (p = 0.05) compared with the placebo or weight maintenance groups. In contrast to our previous findings in postmenopausal women, premenopausal obese women who consume a low calcium diet do not lose bone over a 6-month period, whether their weight is stable or decreasing moderately.

Calorie restriction and skeletal mass in rhesus monkeys (Macaca mulatta): evidence for an effect mediated through changes in body size.

Little is known regarding the effects of prolonged calorie restriction (CR) on skeletal health. We investigated long-term (11 years) and short-term (12 months) effects of moderate CR on bone mass and biochemical indices of bone metabolism in male rhesus monkeys across a range of ages. A lower bone mass in long-term CR monkeys was accounted for by adjusting for age and body weight differences. A further analysis indicated that lean mass, but not fat mass, was a strong predictor of bone mass in both CR and control monkeys. No effect of short-term CR on bone mass was observed in older monkeys (mean age, 19 years), although young monkeys (4 years) subjected to short-term CR exhibited slower gains in total body bone density and content than age-matched controls. Neither biochemical markers of bone turnover nor hormonal regulators of bone metabolism were affected by long-term CR. Although osteocalcin concentrations were significantly lower in young restricted males after 1 month on 30% CR in the short-term study, they were no longer different from control values by 6 months on 30% CR.

A nonhuman primate model of age-related bone loss: a longitudinal study in male and premenopausal female rhesus monkeys.

Aging is associated with gradual bone loss in men and premenopausal women, with an accelerated rate of loss after menopause in women. Although many studies have investigated bone loss due to surgically induced estrogen depletion, little is known regarding normal age-related changes in bone mass in animal models. We used dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD), bone mineral content (BMC), and projected area (PA) at four skeletal sites over 4 years in 20 premenopausal female (8-23 years) and 29 male (8-27 years) rhesus monkeys (Macaca mulatta). Forearm BMD declined with age in both male and female monkeys. Lean mass was positively associated with BMD at all sites in males and with the distal radius in females. Serum osteocalcin declined and urinary cross-links increased with age in males but not females. Serum 25-hydroxyvitamin D concentrations decreased with age in females, and a similar trend was observed in males. In conclusion, an age-related decline in forearm BMD was observed in male and female rhesus monkeys. Total body BMC declined over time in older females, with a similar trend in males. Changes in markers of bone turnover with age were also observed in male monkeys. The results of this longitudinal study suggest that the rhesus monkey is a potential model for age-related changes in the human skeleton.

Energy restriction does not alter bone mineral metabolism or reproductive cycling and hormones in female rhesus monkeys.

Energy restriction (ER) extends the life span and slows aging and age-related diseases in short-lived mammalian species. Although a wide variety of physiological systems have been studied using this paradigm, little is known regarding the effects of ER on skeletal health and reproductive aging. Studies in rhesus monkeys have reported that ER delays sexual and skeletal maturation in young male monkeys and reduces bone mass in adult males. No studies have examined the chronic effects on bone health and reproductive aging in female rhesus monkeys. The present cross-sectional study examined the effects of chronic (6 y) ER on skeletal and reproductive indices in 40 premenopausal and perimenopausal (7-27 y old) female rhesus macaques (Macaca mulatta). Although ER monkeys weighed less and had lower fat mass, ER did not alter bone mineral density, bone mineral content, osteocalcin, 25-hydroxyvitamin D, 1,25-hydroxyvitamin D or parathyroid hormone concentrations, menstrual cycling or reproductive hormone concentrations. Body weight and lean mass were significantly related to bone mineral density and bone mineral content at all skeletal sites (total body, lumbar spine, mid and distal radius; P: < or = 0.04). The number of total menstrual cycles over 2 y, as well as the percentage of normal-length cycles (24-31 d), was lower in older than in younger monkeys (P: < or = 0.05). Older monkeys also had lower estradiol (P: = 0.02) and higher follicle-stimulating hormone (P: = 0.02) concentrations than did younger monkeys. We conclude that ER does not negatively affect these indices of skeletal or reproductive health and does not alter age-associated changes in the same variables.