Osteoporosis: Devine A

Sanders KM, Nowson CA, Kotowicz MA, Briffa K, Devine A, Reid IR, Anonymous00074. · Department of Clinical and Biomedical Sciences, Barwon Health, University of Melbourne, Geelong, VIC, Australia. · Med J Aust. · Pubmed #19296813 No free full text.

Abstract: This position statement was prepared by the Working Group of the Australian and New Zealand Bone and Mineral Society and Osteoporosis Australia. The final statement was endorsed by the Endocrine Society of Australia. Currently, the balance of evidence remains in favour of fracture prevention from combined calcium and vitamin D supplementation in elderly men and women. Adequate vitamin D status is essential for active calcium absorption in the gut and for bone development and remodelling. In adults with a baseline calcium intake of 500-900 mg/day, increasing or supplementing this intake by a further 500-1000 mg/day has a beneficial effect on bone mineral density. Calcium intake significantly above the recommended level is unlikely to achieve additional benefit for bone health.

Ramesh Babu L, Wilson SG, Dick IM, Islam FM, Devine A, Prince RL. · School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia. · Bone. · Pubmed #15777683 No free full text.

Abstract: The pathogenesis of osteoporosis involves both genetic and environmental factors. On the basis of linkage data suggesting gene effects on bone density at chromosome 14q and data locating the BMP4 gene to 14q, we performed a positional candidate study to examine a possible association of BMP4 gene polymorphisms, hip bone density (n = 1012) and fracture rates (n = 1232) in postmenopausal women (mean age 75). On genotype analysis of the three selected single nucleotide polymorphisms (SNP), the 6007C > T polymorphism was associated with total and intertrochanteric hip BMD and BMD was lower in the 32% of subjects homozygous for the C allele. This polymorphism codes for a nonsynonymous amino acid change with the T allele coding for valine, while the C allele codes for alanine. The difference in BMD was 3.1% (TT vs. CC) and 2.3% (CT versus CC) for the total hip (P = 0.023), and 3.7% (TT vs. CC) and 2.8% (CT versus CC) for the intertrochanter site (P = 0.012). Haplotype analysis demonstrated 6 haplotypes of frequency greater than 2%. A major haplotype defined by G-C-T alleles in SNPs -5826G > A, 3564C > T and 6007C > T respectively, showed association with high bone mass. No SNP showed association with fracture rates. We conclude that a polymorphism found in the BMP4 gene, affecting amino acid sequence, is associated with hip bone density in postmenopausal women, presumably via regulation of anabolic effects on the skeleton.

Dick IM, Devine A, Prince RL. · School of Medicine and Pharmacology, Univ. of Western Australia, 4th Floor G Block, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia. · Am J Physiol Endocrinol Metab. · Pubmed #15613678 links to  free full text

Abstract: Osteoporosis is a disease that is strongly genetically determined. Aromatase converts androgens to estradiol in postmenopausal women, therefore polymorphisms of the gene for this enzyme may be associated with bone mass and fracture. We investigated the association of the TTTA microsatellite polymorphism in intron 4 of the aromatase (CYP19) gene with bone mineral density (BMD) and fracture in 1,257 women aged 70 yr and greater. The data obtained were stratified based on the presence or absence of a [TTTA]n of 7 (A2), determined from a preliminary analysis of hip dual-energy X-ray absorptiometry BMD, which was present in 27% of the population. The presence of an A2 allele was associated with a higher free estradiol index (0.52 +/- 0.49, P = 0.049) compared with the absence of an A2 allele (0.47 +/- 0.45); higher BMD at all sites of the hip (3.4% total hip, 2.3% femoral neck, 3.6% intertrochanter, 4.1% trochanter) and the lumbar spine (12.7%); higher values for the calcaneal quantitative ultrasound parameters broadband ultrasound (1.3%), speed of sound (0.4%), and stiffness (3.7%); and higher peripheral quantitative computed tomography measures for total (3.4%), trabecular (3.3%), and cortical BMD (3.3%) and the derived stress strain index (SSI) parameters SSI polar (6.4%) and SSI x (6.8%) values. A lower deoxypryridinoline creatinine ratio was observed in subjects with an A2 allele (30.3 +/- 10.4 vs. 27.1 +/- 9.1, P = 0.03). The A2 allele was associated with a lower prevalence of vertebral fracture in subjects who were osteoporotic (odds ratio 0.27, confidence interval 0.09-0.79). Therefore, a common polymorphism of the aromatase gene, perhaps in linkage disequilibrium with a functionally significant CYP19 polymorphism, is associated with bone structure and bone turnover, either by local effects or by effects on circulating bioactive estrogen.

Dick IM, Devine A, Beilby J, Prince RL. · School of Medicine and Pharmacology, Univ. of Western Australia, 4th Floor G Block, Sir Charles Gairdner Hospital, Nedlands, WA, Australia 6009. · Am J Physiol Endocrinol Metab. · Pubmed #15466921 links to  free full text

Abstract: High postmenopausal endogenous estrogen concentrations are an important determinant of preservation of bone mass and reduced fracture in elderly women. Calcium supplementation can also reduce bone loss in these patients, suggesting an interaction between estrogen deficiency and calcium balance. Potential mechanisms of estrogen on calcium transport include direct effects on the bone, the kidney, and the bowel. Previous studies have demonstrated effects of estrogen on renal phosphate handling. We have used a cross-sectional, population-based analysis of biochemical data obtained from ambulant elderly women to determine the association of endogenous estradiol with urine calcium and phosphorus excretion. The subjects were 293 postmenopausal women >70 yr old. Factors associated with renal calcium and phosphate excretion were measured, including the filtered calcium and phosphate load, parathyroid hormone (PTH), estradiol, and sex hormone-binding globulin (SHBG). The free estradiol concentration (FE) was calculated from a previously described formula. A high plasma estradiol concentration (r(2) = 0.023, P = 0.01) and a high FE (r(2) = 0.045, P = 0.001) were associated with reduced renal calcium excretion. The estradiol and FE effect on renal calcium excretion remained significant after adjusting for calcium filtered at the glomerulus and serum PTH. A high FE was associated with a reduced renal phosphate threshold in univariate analysis (r(2) = 0.023, P = 0.010). The effect remained significant after adjustment for serum PTH. The size of the effect of the FE was of the same order of magnitude as the effect of PTH on reducing renal calcium excretion and increasing renal phosphate excretion. These data support in vitro and animal data demonstrating an effect of estradiol on renal calcium and phosphate handling and indicate that, in elderly postmenopausal women, the effect is of a similar magnitude to the well-recognized effects of PTH on these physiologically regulated parameters.

Devine A, Dick IM, Dhaliwal SS, Naheed R, Beilby J, Prince RL. · School of Medicine and Pharmacology, Sir Charles Gairdner Hospital, University of Western Australia, 4th Floor G Block, 6009, Nedlands, Western Australia, Australia. <> · Osteoporos Int. · Pubmed #15197544 No free full text.

Abstract: A decline in postmenopausal estrogen concentration accelerates postmenopausal bone loss. We have examined the predictive power of endogenous estrogen production, DXA hip bone density (BMD), and heel quantitative ultrasound (QUS) on incident clinical fracture in a prospective 3-year population based, randomised controlled trial of calcium supplementation. Baseline blood testing on 1499 women mean (SD) age 75 (3) years for estradiol and sex hormone binding globulin measurements and ankle QUS measurements (Lunar Achilles) was undertaken. Bone density was measured using DXA (Hologic 4500A) at 1 year. Incident clinical fractures were confirmed by X-ray. At 3 years, 10% had sustained more than one incident fracture. The fracture group had significantly lower levels of free estradiol index (FEI) (0.40+/-0.44 versus 0.49+/-0.54 pmol/nmol), hip BMD (0.776+/-0.129 versus 0.815+/-0.124 g/cm(2)) and measures of QUS (BUA 98+/-8 versus 101+/-8 db/Hz, SOS 1504+/-22 versus 1514 +/-26 m/s; stiffness 67+/-11 versus 71+/-11 % mean young adult), respectively, than the non-fracture group. After adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture, incident fracture was predicted by free estradiol index (HR per SD: 1.43:95%CI: 1.08-1.91, P=0.013). After adjustment for BMD, SOS or stiffness, the free estradiol index no longer predicted fracture. When examined separately, the presence of a vertebral or an appendicular fracture was associated with an 18% lower free estradiol index compared with no fracture. The risk of vertebral fracture increased with decreased free estradiol index (HR per SD reduction: 1.63:95% CI: 0.91-2.92); the risk of appendicular fracture also increased with decreased free estradiol index (HR per SD reduction: 1.45:95% CI: 1.05-2.01) after adjustment for age, weight, use of topical estrogen, calcium supplementation and prevalent fracture. After further adjustment for hip BMD or QUS measures, the effect of free estradiol index was no longer significant for vertebral or appendicular fractures. Therefore, a low free estradiol index increases the probability of having an incident fracture as a result of decreased BMD. These data confirm the importance of postmenopausal estrogen concentration in the pathogenesis of osteoporosis in elderly women.

Zhu K, Devine A, Prince RL. · Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. · Osteoporos Int. · Pubmed #18575949 No free full text.

Abstract: SUMMARY: Few studies have investigated the long-term effects of potassium intake on BMD. In a cohort of 266 elderly women, we found that baseline potassium intake as reflected by 24-hour urine potassium excretion had positive association with BMD measured at 1 and/or 5 years later, suggesting a role of dietary potassium on osteoporosis prevention. INTRODUCTION: High dietary potassium intake has been suggested to be beneficial for bone structure, but few studies have investigated the long-term effects of potassium intake on BMD in elderly women. We examined the relationship between potassium intake as reflected by 24-hour urine potassium excretion and bone density in a cohort of elderly women. METHODS: The study subjects were 266 elderly postmenopausal women aged 70-80 years. Twenty-four-hour urinary potassium excretion was determined at baseline. At one year hip DXA BMD was measured, at 5 years hip and total body DXA BMD and distal radius and tibia pQCT vBMD were measured. The effects of potassium were evaluated by ANCOVA according to the quartile of baseline urinary potassium excretion. RESULTS: After adjustment for confounding factors, subjects in the highest quartile of urinary potassium excretion had significantly higher total hip BMD at 1 (5%) and 5 years (6%), and significantly higher total body BMD (4%) and 4% distal tibia total (7%) and trabecular vBMD (11%) at 5 years than those in the lowest quartile. CONCLUSIONS: Potassium intake shows positive association with bone density in elderly women, suggesting that increasing consumption of food rich in potassium may play a role in osteoporosis prevention.

Hodgson JM, Devine A, Burke V, Dick IM, Prince RL. · Royal Perth Hospital Unit, the University of Western Australia School of Medicine and Pharmacology, Perth, Australia. · Am J Clin Nutr. · Pubmed #18175753 links to  free full text

Abstract: BACKGROUND: Nutrition is important for the development and maintenance of bone structure and for the prevention of osteoporosis and fracture. The relation of chocolate intake with bone has yet to be investigated. OBJECTIVE: We investigated the relation of chocolate consumption with measurements of whole-body and regional bone density and strength. DESIGN: Randomly selected women aged 70-85 y (n=1460) were recruited from the general population to a randomized controlled trial of calcium supplementation and fracture risk. We present here a cross-sectional analysis of 1001 of these women. Bone density and strength were measured with the use of dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography. Frequency of chocolate intake was assessed with the use of a questionnaire and condensed into 3 categories: <1 time/wk, 1-6 times/wk, >or=1 time/d. RESULTS: Higher frequency of chocolate consumption was linearly related to lower bone density and strength (P<0.05). Daily (>or=1 times/d) consumption of chocolate, in comparison to <1 time/wk, was associated with a 3.1% lower whole-body bone density; with similarly lower bone density of the total hip, femoral neck, tibia, and heel; and with lower bone strength in the tibia and the heel (P<0.05, for all). Adjustment for covariates did not influence interpretation of the results. CONCLUSIONS: Older women who consume chocolate daily had lower bone density and strength. Additional cross-sectional and longitudinal studies are needed to confirm these observations. Confirmation of these findings could have important implications for prevention of osteoporotic fracture.

Mullin BH, Prince RL, Dick IM, Islam FM, Hart DJ, Spector TD, Devine A, Dudbridge F, Wilson SG. · Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, 6009. · Osteoporos Int. · Pubmed #18038243 No free full text.

Abstract: SUMMARY: The 1p36 region of the human genome has been identified as containing a QTL for BMD in multiple studies. We analysed the TNFRSF1B gene from this region, which encodes the TNF receptor 2, in two large population-based cohorts. Our results suggest that variation in TNFRSF1B is associated with BMD. INTRODUCTION: The TNFRSF1B gene, encoding the TNF receptor 2, is a strong positional and functional candidate gene for impaired bone structure through the role that TNF has in bone cells. The aims of this study were to evaluate the role of variations in the TNFRSF1B gene on bone structure and osteoporotic fracture risk in postmenopausal women. METHODS: Six SNPs in TNFRSF1B were analysed in a cohort of 1,190 postmenopausal Australian women, three of which were also genotyped in an independent cohort of 811 UK postmenopausal women. Differences in phenotypic means for genotype groups were examined using one-way ANOVA and ANCOVA. RESULTS: Significant associations were seen for IVS1+5580A>G with BMD and QUS parameters in the Australian population (P = 0.008 - 0.034) and with hip BMD parameters in the UK population (P = 0.005 - 0.029). Significant associations were also observed between IVS1+6528G>A and hip BMD parameters in the UK cohort (P = 0.0002 - 0.003). We then combined the data from the two cohorts and observed significant associations between both IVS1+5580A>G and IVS1+6528G>A and hip BMD parameters (P = 0.002 - 0.033). CONCLUSIONS: Genetic variation in TNFRSF1B plays a role in the determination of bone structure in Caucasian postmenopausal women, possibly through effects on osteoblast and osteoclast differentiation.

Devine A, Hodgson JM, Dick IM, Prince RL. · Nutrition Program, School of Exercise, Biomedical and Health Science, Edith Cowan University, 100 Joondalup Drive, Joondalup WA 6027 Australia. · Am J Clin Nutr. · Pubmed #17921409 links to  free full text

Abstract: BACKGROUND: Impaired hip structure assessed by dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD) is an independent predictor for osteoporotic hip fracture. Some studies suggest that tea intake may protect against bone loss. OBJECTIVE: Using both cross-sectional and longitudinal study designs, we examined the relation of tea consumption with hip structure. DESIGN: Randomly selected women (n = 1500) aged 70-85 y participated in a 5-y prospective trial to evaluate whether oral calcium supplements prevent osteoporotic fractures. aBMD at the hip was measured at years 1 and 5 with DXA. A cross-sectional analysis of 1027 of these women at 5 y assessed the relation of usual tea intake, measured by using a questionnaire, with aBMD. A prospective analysis of 164 women assessed the relation of tea intake at baseline, measured by using a 24-h dietary recall, with change in aBMD from years 1 to 5. RESULTS: In the cross-sectional analysis, total hip aBMD was 2.8% greater in tea drinkers (x: 806; 95% CI: 797, 815 mg/cm(2)) than in non-tea drinkers (784; 764, 803 mg/cm(2)) (P < 0.05). In the prospective analysis over 4 y, tea drinkers lost an average of 1.6% of their total hip aBMD (-32; -45, -19 mg/cm(2)), but non-tea drinkers lost 4.0% (-13; -20, -5 mg/cm(2)) (P < 0.05). Adjustment for covariates did not influence the interpretation of results. CONCLUSION: Tea drinking is associated with preservation of hip structure in elderly women. This finding provides further evidence of the beneficial effects of tea consumption on the skeleton.

Ueland T, Bollerslev J, Wilson SG, Dick IM, Islam FM, Mullin BH, Devine A, Prince RL. · Section of Endocrinology, Rikshospitalet University Hospital, Oslo, Norway. · Bone. · Pubmed #16949901 No free full text.

Abstract: Bone mass is the single most important risk factor for osteoporotic fractures in the elderly and is mainly influenced by genetic factors accounting for 40-75% of the inter-individual variation. Critical for the bone remodeling process is the balance between the newly discovered members of the tumor necrosis factor ligand and receptor superfamilies, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand, which mediate the effects of many upstream regulators of bone metabolism. In the present study, we evaluated the impact of sequence variations in the OPG gene on bone mass, bone-related biochemistry including serum OPG and fracture frequency in elderly Australian women. A total of 1101 women were genotyped for 3 different single nucleotide polymorphisms (SNP) within the OPG gene (G1181C, T950C and A163G). The effects of these SNPs and serum OPG on calcaneal quantitative ultrasound measurements, osteodensitometry of the hip and bone-related biochemistry were examined. We found no significant relationship between sequence variations in the OPG gene or serum OPG and bone mass, bone-related biochemistry or fracture frequency. Our findings confirm some recent publications investigating the same SNPs but diverge from others, indicating that generalization of the relationships found in this type of study must be done with caution and signify the importance of determining associations between polymorphisms and osteoporosis in different ethnic groups.

Prince RL, Devine A, Dhaliwal SS, Dick IM. · School of Medicine and Pharmacology, University of Western Australia, Australia. · Arch Intern Med. · Pubmed #16636212 links to  free full text

Abstract: BACKGROUND: Increased dietary calcium intake has been proposed as a population-based public health intervention to prevent osteoporotic fractures. We have examined whether calcium supplementation decreases clinical fracture risk in elderly women and its mechanism of action. METHODS: Five-year, double-blind, placebo-controlled study of 1460 women recruited from the population and older than 70 years (mean age, 75 years) who were randomized to receive calcium carbonate, 600 mg twice per day, or identical placebo. The primary end points included clinical incident osteoporotic fractures, vertebral deformity, and adverse events ascertained in 5 years. Bone structure was also measured using dual x-ray absorptiometry of the hip and whole body, quantitative ultrasonography of the heel, and peripheral quantitative computed tomography of the distal radius. RESULTS: Among our patients, 16.1% sustained 1 or more clinical osteoporotic fractures. In the intention-to-treat analysis, calcium supplementation did not significantly reduce fracture risk (hazard ratio, 0.87; 95% confidence interval, 0.67-1.12). However, 830 patients (56.8%) who took 80% or more of their tablets (calcium or placebo) per year had reduced fracture incidence in the calcium compared with the placebo groups (10.2% vs 15.4%; hazard ratio, 0.66; 95% confidence interval, 0.45-0.97). Calcium-treated patients had improved quantitative ultrasonography findings of the heel, femoral neck and whole-body dual x-ray absorptiometry data, and bone strength compared with placebo-treated patients. Of the 92 000 adverse events recorded, constipation was the only event increased by the treatment (calcium group, 13.4%; placebo group, 9.1%). CONCLUSION: Supplementation with calcium carbonate tablets supplying 1200 mg/d is ineffective as a public health intervention in preventing clinical fractures in the ambulatory elderly population owing to poor long-term compliance, but it is effective in those patients who are compliant.

Mullin BH, Wilson SG, Islam FM, Calautti M, Dick IM, Devine A, Prince RL. · Dept. of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Western Australia, Australia. · Calcif Tissue Int. · Pubmed #16151675 No free full text.

Abstract: Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization--Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c.1775G>A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c>t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G>A SNP site and a haplotype including this are associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of "rescue" by other genetic or environmental factors in this population.

Devine A, Dick IM, Islam AF, Dhaliwal SS, Prince RL. · School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. · Am J Clin Nutr. · Pubmed #15941897 links to  free full text

Abstract: BACKGROUND: The effect of protein intake on bone density is uncertain, and evidence exists for beneficial effects of both low and high protein intakes. OBJECTIVE: The objective was to study the relation between protein consumption and bone mass in elderly women with allowance for other lifestyle factors affecting bone metabolism. DESIGN: We conducted a cross-sectional and longitudinal study of a population-based sample of 1077 women aged 75 +/- 3 y. At baseline, protein consumption was measured with a food-frequency questionnaire, and bone mass and structure were measured by using quantitative ultrasound of the heel. One year later, hip bone mineral density (BMD) was measured by using dual-energy X-ray absorptiometry. RESULTS: Subjects consumed a mean (+/-SD) of 80.5 +/- 27.8 g protein/d (1.19 +/- 0.44 g protein/kg body wt). Regression analysis showed a positive correlation between protein intake and qualitative ultrasound of the heel and BMD after adjustment for age, body mass index, and other nutrients. The dose-response effect was best characterized by protein consumption expressed in tertiles, such that subjects in the lowest tertile (<66 g protein/d) had significantly lower qualitative ultrasound of the heel (1.3%) and hip BMD (2.6%) than did the subjects in the higher tertiles (>87 g protein/d). CONCLUSION: These data suggest that protein intakes for elderly women above current recommendations may be necessary to optimize bone mass.

Bollerslev J, Wilson SG, Dick IM, Islam FM, Ueland T, Palmer L, Devine A, Prince RL. · School of Medicine and Pharmacology, University of Western Australia, Nedlands. · Bone. · Pubmed #15777745 No free full text.

Abstract: Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exon 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357 A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-up period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures.

Devine A, Dhaliwal SS, Dick IM, Bollerslev J, Prince RL. · School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia. · J Bone Miner Res. · Pubmed #15355558 No free full text.

Abstract: A population-based study of 1363 older women showed that the 24% who achieved high physical activity and dietary calcium intakes had a 5.1% higher hip BMD than those who did not, supporting the concept that lifestyle factors play an important role in the maintenance of lower extremity bone mass in older women. INTRODUCTION: Although there is general agreement that increased dietary calcium consumption and exercise can slow bone loss in older women, the amount required to have this effect in an older population remains uncertain. This study was devised to examine the effects of calcium consumption (CC) and physical activity (PA) (lifestyle management) on bone mass in an older female population. MATERIALS AND METHODS: Using a cross-sectional study design, a population-based sample of older women (mean age, 75 +/- 3 years) had hip and heel bone mass measured using DXA (Hologic 4500A; n = 1076) and quantitative ultrasound (QUS, Lunar Achilles; n = 1363), respectively. CC and PA were measured by a validated habitual food frequency and activity questionnaire, respectively. Dose-response effects of PA and CC on bone mass were examined using ANOVA. RESULTS AND CONCLUSIONS: Division of the PA and CC into tertiles best described the dose-response effects. After adjustment for CC, age, weight, alcohol consumption, and cigarette smoking, high PA compared with medium or low PA was associated with higher hip BMD and heel QUS (total hip BMD, 3.1%; p < 0.001; QUS stiffness, 2.7%; p = 0.002). After adjustment for PA and covariates, high or medium CC compared with low CC was associated with higher total hip BMD (1.8%; p = 0.027), with no effect at the QUS heel site. PA and CC were dichotomized at the cut-points for effects on BMD. The combination of high PA and CC, achieved by 24% of the population, was associated with a total hip BMD that was 5.1% higher (34% of SD) than those individuals in the low PA and CC group. Stiffness was 3.6% (23% of SD) higher in the high PA and CC group than in the low PA and CC group. If the whole population undertook and achieved a high PA and high CC lifestyle, the population risk of hip fractures may be expected to be reduced by about 17% in this age group as a result of beneficial effects on the musculoskeletal system.

Bollerslev J, Wilson SG, Dick IM, Devine A, Dhaliwal SS, Prince RL. · School of Medicine and Pharmacology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. · Calcif Tissue Int. · Pubmed #14508624 No free full text.

Abstract: Postmenopausal osteoporosis is a complex and heterogeneous disease influenced by multiple factors and related to peak bone mass achieved in early adult life, followed by a subsequent continuous bone loss. Genetic variance and polymorphisms have been shown to be of clinical significance for osteoporotic fragility fractures. Previous studies have related variations in the calcium sensor receptor (CASR) gene to circulating Ca levels and bone mass in young women and adolescent girls. The aim of this study was to investigate the impact of the A986S polymorphism of the CASR gene on calcium homeostasis and bone metabolism in elderly women. We studied the distribution of the A986S polymorphism in a large cohort of 1252 ambulatory Australian women in relation to biochemical markers of bone metabolism, bone mass evaluated by quantitative ultrasound measurements (QUS) and DXA of the hip, prevalent and 36-month incident fracture data. No effect of the polymorphism was found on circulating calcium level, renal Ca excretion, or biochemical markers of bone turnover. Moreover, A986S was not associated with bone mass or prevalent or incident fractures. Power calculations revealed that a difference in circulating calcium levels of 0.05 mmol/l, a difference in DXA bone density of 24 mg, and a 1.6-fold difference in fracture rate could have been detected with a power of 80%. In conclusion, in a large cohort of elderly women the A986S polymorphism of the CASR gene was not found to be significant for calcium homeostasis or bone mass. It is questioned whether the polymorphism has any clinical significance for postmenopausal osteoporosis.

Dick IM, Devine A, Li S, Dhaliwal SS, Prince RL. · Department of Medicine, Sir Charles Gairdner Hospital, University of Western Australia, Nedlands, WA, Australia. · Bone. · Pubmed #13678774 No free full text.

Abstract: Osteoporosis is a disease that is strongly genetically determined and polymorphisms present in a range of candidate genes may be involved. A number of previous studies have shown an association between the T869C functional polymorphism of the gene for transforming growth factor beta (TGF beta) and bone mineral density (BMD) and fracture, but these studies have been limited to relatively small studies of selected subjects. In a population-based study of 1337 white women over age 70 we examined the TGF beta T869 polymorphism in relation to BMD, calcaneal quantitative ultrasound (QUS), and prevalent and incident fracture. The TGF beta C allele was observed in 50% of the subjects and was associated with reduced hip BMD at all sites (2.8% total hip, 2.4% femoral neck, 2.6% intertrochanter, and 3.4% trochanter) compared to the TGF beta TT genotype. The TGF beta C allele was also associated with a reduction in the QUS parameters BUA, SOS, and stiffness of 0.87%, 0.26%, and 2.4%, respectively, compared to the TGF beta TT genotype. After adjustment for body mass index in an analysis of variance model, the effect of the TGF beta C allele remained significant at the total hip, the femoral neck, and the trochanter, and for the QUS SOS and stiffness parameters. The TGF beta C allele was associated with an increase in osteoporosis [T score < or =-2.5 SD; odds ratio (OR) 2.07; 95% confidence interval (CI) 1.19-3.60] and prevalent fracture (1.37; 95% CI 1.06-1.75). After adjustment for BMD and QUS stiffness, the association of the TGF beta C allele with prevalent fracture was still present (OR 1.40; 95% CI 1.04-1.89), suggesting that the effect of the C allele on fracture was independent of a reduction in BMD and QUS stiffness. Subjects with normal BMD and a TGF beta C allele had an increased risk of incident fracture over 3 years compared to subjects with normal BMD and a TGF beta TT genotype (relative risk 3.95; 95% CI 1.52-10.29). This association was not found in osteopenic or in osteoporotic subjects, indicating a BMD-TGF beta C allele interaction in relation to the association of the TGF beta C allele with fracture risk. These findings are of potential clinical usefulness, as the TGF beta T869C genotype could be used, in conjunction with other genetic and clinical information, to determine an individual's risk of osteoporosis.