Osteoporosis: Kotowicz MA

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.

Ebeling PR, Wark JD, Yeung S, Poon C, Salehi N, Nicholson GC, Kotowicz MA. · Department of Diabetes, University of Melbourne Hospital, Melbourne, Parkville 3050, Australia. · J Clin Endocrinol Metab. · Pubmed #11549632 links to  free full text

Abstract: Osteoporosis in men is an emerging public health problem. As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women, we conducted a prospective study of this treatment in men with primary osteoporosis. Our study was a 2-yr, randomized, double masked, double placebo-controlled trial of calcitriol (0.25 microg twice daily) or calcium (500 mg twice daily) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture. Thirty-three men (85%) completed the study. There were no differences in baseline characteristics. Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups. Serum osteocalcin decreased in both groups by 30% (P < 0.05), whereas urine N-telopeptide cross-links decreased only in the calcium group by 30% (P < 0.05). After 2 yr, fractional calcium absorption increased by 34% (P < 0.01) in the calcitriol group. Nineteen incident fragility fractures occurred (14 vertebral and 5 nonvertebral) in 7 men. Over 2 yr, the number of men with vertebral fractures (6 vs. 1; P = 0.097) was similar in both groups. In conclusion, the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men.

Pasco JA, Henry MJ, Nicholson GC, Brennan SL, Kotowicz MA. · Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Australia. · Bone. · Pubmed #19264157 No free full text.

Abstract: For most people in Australia, the primary source of vitamin D is casual exposure to sunlight. Hypovitaminosis D has been reported for high-risk populations, but little has been documented for women of all ages living in the community. Using cross-sectional data, we aimed to describe physical and behavioural characteristics associated with serum 25-hydroxyvitamin D (25OHD) for such women and to determine the association of serum 25OHD with hypertension and bone health. Serum 25OHD, parathyroid hormone (PTH), blood pressure, bone mineral density (BMD) and anthropometry were measured in a random sample of 861 women aged 20-92 years enrolled in the Geelong Osteoporosis Study, set in a temperate region at latitude 38-39 degrees S. Lifestyle factors (including diet, smoking, medication use, socio-economic status, residence, education, occupation, and physical activity) were documented by questionnaire. In season-adjusted models for women aged 20-54 years, physical activity and living with a partner were independently and positively associated with serum 25OHD; associations with weight and waist-hip ratio were negative. Among older women, physical activity, vitamin D intake and urban dwelling were positively associated with serum 25OHD; age, weight and smoking were negative. Compared with the lowest tertile, those in the highest serum 25OHD tertile were less likely to have elevated serum PTH (adjusted OR=0.25, 95% CI 0.16-0.41) and high blood pressure (adjusted OR=0.40, 95% CI 0.22-0.72), and more likely to have normal hip and spine BMD (adjusted OR=1.65, 95% CI 1.08-2.52). In multivariable models adjusting for season, age, weight (and height), BMD was associated with serum 25OHD at the spine, hip and whole body; no associations were detected at the forearm and no other characteristics were identified as confounders. Factors associated with high vitamin D status generally reflected healthy body habitus and active lifestyles. In contrast, excessive weight and smoking were associated with poorer vitamin D status. Women with high vitamin D were less likely to have elevated PTH, hypertension or bone deficits than women with poor levels.

Pasco JA, Henry MJ, Korn S, Nicholson GC, Kotowicz MA. · Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Australia. · Osteoporos Int. · Pubmed #18802658 No free full text.

Abstract: The epidemiology and sequelae of morphometric vertebral fracture (MVF) are poorly documented. We found that MVFs of the lower thoracic and lumbar spine were associated with poor quality of life and impaired physical function in men. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry. INTRODUCTION: Vertebral fractures are sentinel events for osteoporosis. We aimed to compare quality of life and physical function in men with and without MVF. METHODS: Using morphometric X-ray absorptiometry (T10-L4), MVFs were identified in a random sample of men aged 20-93 years. Moderate and severe wedge, biconcave or compression deformities (>25% reduction in any vertebral height) were classified as MVFs. RESULTS: Of 1,147 men, MVFs were identified in 64. No MVFs were detected for men in their twenties. Prevalence was 1.5% for 30-39 years, 1.4% 40-49 years, 3.2% 50-59 years, 4.7% 60-69 years, 10.0% 70-79 years and 14.6% 80+ years. Among 555 men aged 60+ years, those with MVFs were twice as likely to have quality of life scores in the lowest tertile (age-adjusted OR = 2.35, 95%CI 1.24-4.45). MVFs were associated with lower mean age-adjusted physical activity scores [11.3 (95%CI 9.0-13.8) vs 14.0 (13.2-14.9), P = 0.04] and longer mean age-adjusted 'Up-&-Go' times [9.5 (8.9, 10.1) vs 8.9 (8.8, 9.1) s, P = 0.06]. CONCLUSION: Despite most men being unaware of their condition, MVFs were associated with poor quality of life and impaired physical function. We recommend that morphometric X-ray absorptiometry be included in routine requests for bone densitometry because detection of MVFs has important implications for osteoporosis management in men.

Henry MJ, Pasco JA, Sanders KM, Kotowicz MA, Nicholson GC. · Department of Clinical and Biomedical Sciences, Barwon Health, The University of Melbourne, Victoria, Australia. · J Clin Densitom. · Pubmed #18619881 No free full text.

Abstract: In Australia, benefits for antifracture therapies have been available for patients with osteoporosis and a prior fracture. No benefits were available to those with no prior fracture. We aimed to define, in women with no prior fracture, age-related thresholds of bone mineral density (BMD) associated with fracture risk equivalent to that of women with prior fracture and osteoporosis. A case-control study of women (> or =50 yr) was conducted, including 291 fracture cases and 823 controls. BMD was measured at the proximal femur and posterior anterior (PA) spine. A fracture risk score (FRS) for the group with no prior fracture was calculated with discriminant analysis. The thresholds for equivalent fracture risk between those with no prior fracture and those with prior fracture were assessed using logistic regression. Increasing the FRS to +0.98 in women with no prior fracture resulted in equivalent odds of sustaining a fracture to those with prior fracture and osteoporosis. The corresponding T-score thresholds at the spine were -4.6 at 50 yr, -3.9 at 60 yr, -3.1 at 70 yr, and -2.4 at 80 yr. The femoral neck T-score thresholds were lower by 0.5 standard deviation. The high-risk individuals defined by this study should be considered for primary fracture prevention therapy.

Henry MJ, Pasco JA, Sanders KM, Nicholson GC, Kotowicz MA. · Department of Clinical and Biomedical Sciences, the University of Melbourne, Barwon Health, PO Box 281, Geelong 3220, Victoria, Australia. · Radiology. · Pubmed #16928979 links to  free full text

Abstract: PURPOSE: To develop and evaluate a fracture risk (FRISK) score based on multiple-site bone mineral density (BMD) measurements and other risk factors, to enable prediction of future fracture occurrence. MATERIALS AND METHODS: All participants gave written informed consent, and the study was approved by the Barwon Health Research and Ethics Advisory Committee. BMD was measured at the femoral neck and spine in two concurrently recruited groups: women 60 years of age or older who had sustained a low-trauma fracture of the hip, spine, humerus or distal forearm during a 2-year ascertainment period (n = 231; mean age, 74 years +/- 7 [standard deviation]) and a population-based random sample of women who had not sustained a fracture during the recruitment period (n = 448; mean age, 72 years +/- 8). Falls in the previous year and the number of self-reported fractures in adult life were recorded. Coefficients of a multiple logistic regression model were used as weightings for a combined model. A longitudinal population-based sample was used to assess the fracture risk equation (n = 600; median age, 74 years; interquartile range, 67-82 years). RESULTS: The FRISK score was obtained from the following equation: 9.304 - 4.735BMD(SP) - 4.530BMD(FN) + 1.127FS + 0.344NPF + 0.037W, where BMD(SP) is spinal BMD (in grams per square centimeter), BMD(FN) is femoral neck BMD, FS is falls score, NPF is number of previous fractures, and W is weight (in kilograms). The FRISK score successfully predicted 75% of fractures 2 years after baseline measurements in subjects in the longitudinal study with 68% specificity. CONCLUSION: This study resulted in the derivation of a fracture risk score that successfully predicted 75% of fractures 2 years after baseline.

Pasco JA, Seeman E, Henry MJ, Merriman EN, Nicholson GC, Kotowicz MA. · Department of Clinical and Biomedical Sciences, Barwon Health, The Geelong Hospital, The University of Melbourne, P.O. Box 281, Geelong 3220, Australia. · Osteoporos Int. · Pubmed #16699736 No free full text.

Abstract: INTRODUCTION: Osteoporosis is associated with increased risk for fracture. However, most postmenopausal women have bone mineral density (BMD) within the normal or osteopenic range. The aim of this study was to determine the proportion of the population burden of fragility fractures arising from women at modest risk for fracture. METHODS: We measured baseline BMD in a population-based random sample of 616 postmenopausal women aged 60-94 years and followed these individuals for a median of 5.6 years (IQR 3.9-6.5) to determine the incidence of fractures according to age, BMD and the presence of a prior fracture. RESULTS: Based on WHO criteria, 37.6% of the women had normal total hip BMD, 48.0% had osteopenia and 14.5% had osteoporosis. The incidence of fracture during follow-up was highest in women with osteoporosis, but only 26.9% of all fractures arose from this group; 73.1% occurred in women without osteoporosis (56.5% in women with osteopenia, 16.6% in women with normal BMD). Decreasing BMD, increasing age and prior fracture contributed independently to increased fracture risk; in a multivariate model, the relative risk for fracture increased 65% for each SD decrease in BMD (RR=1.65, 95%CI 1.32-2.05), increased 3% for every year of age (RR=1.03, 95%CI 1.01-1.06) and doubled with prevalent fracture (RR=2.01, 95% CI 1.40-2.88). A prevalent fracture increased the risk for fractures such that women with osteopenia and prevalent fracture had the same, if not greater, risk as women with osteoporosis alone. CONCLUSIONS: Reducing the population burden of fractures requires attention to women with osteopenia, as well as osteoporosis, because over half of the fragility fractures in the population arise in these individuals, and women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis.

Pasco JA, Henry MJ, Wilkinson LK, Nicholson GC, Schneider HG, Kotowicz MA. · The University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, Geelong, Victoria, Australia. · J Womens Health (Larchmt). · Pubmed #16620188 No free full text.

Abstract: BACKGROUND: Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover. METHODS: In an observational study of 533 randomly selected women, we investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD). RESULTS: Twenty-two women were identified as current users of supplemental vitamin C or E. Duration of antioxidant supplement use was negatively associated with age-adjusted and weight-adjusted serum CTx, such that mean CTx levels (natural log transformed) were 0.022 units lower for each year of exposure. No significant differences were detected for adjusted serum BSAP or whole body BMD. CONCLUSIONS: Our results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.

Sanders KM, Nicholson GC, Watts JJ, Pasco JA, Henry MJ, Kotowicz MA, Seeman E. · Department of Clinical and Biomedical Sciences, Barwon Health, The University of Melbourne, PO Box 281, Geelong 3220, Australia. · Bone. · Pubmed #16507356 No free full text.

Abstract: To determine the age- and BMD-specific burden of fractures in the community and the cost-effectiveness of targeted drug therapy, we studied a demographically well-categorized population with a single main health provider. Of 1224 women over 50 years of age sustaining fractures during 2 years, the distribution of all fractures was 11%, 20%, 33%, and 36% in those aged 50-59, 60-69, 70-79, and 80+ years, respectively. Osteoporosis (T score < -2.5) was present in 20%, 46%, 59%, and 69% in the respective age groups. Based on this sample and census data for the whole country, treating all women over 50 years of age in Australia with a drug that halves fracture risk in osteoporotic women and reduces fractures in those without osteoporosis by 20%, was estimated to prevent 18,000 or 36% of the 50,000 fractures per year at a total cost of $573 million (AUD). Screening using a bone mineral density of T score of -2.5 as a cutoff, misses 80%, 54%, 41%, and 31% of fractures in women in the respective age groups. An analysis of cost per averted fracture by age group suggests that treating women in the 50- to 59-year age group with osteoporosis alone costs $156,400 per averted fracture. However, in women aged over 80 years, the cost per averted fracture is $28,500. We infer that treating all women over 50 years of age is not feasible. Using osteoporosis and age (>60 years) as criteria for intervention reduces the population burden of fractures by 28% and is cost-effective but solutions to the prevention of the remaining 72% of fragility fractures remain unavailable.

Pasco JA, Sanders KM, Hoekstra FM, Henry MJ, Nicholson GC, Kotowicz MA. · University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, P.O. Box 281, 3220, Geelong, Victoria, Australia. · Osteoporos Int. · Pubmed #16228106 No free full text.

Abstract: In this population-based, observational study, we document the personal burden of fracture and utilization of community and health services for women during the 12-month period following a fracture. Participants were 598 women (aged 35-92 years) with incident fracture in the years 1994-1996 who were enrolled in the Geelong Osteoporosis Study. Almost all hip fracture cases and 27% of nonhip fracture cases were hospitalized. Homes were modified in 14% of cases, and 32% of the women purchased or hired equipment to assist with activities of daily living. Three-quarters of women with hip, pelvis, or lower limb fractures were confined to the home, had to walk with a walking aid, or could walk only short distances for several weeks. After a year, nearly one-half had not regained prefracture mobility. One-seventh of women with upper-limb fractures did not venture outside the home for at least 6 weeks. Nearly half of all fracture cases needed help with personal care and housework during the first 6 weeks. After 6 months, 3.4% of all patients and 19.6% of hip, 12.8% of humeral, and 4.7% of spine fracture patients required assistance with bathing and showering. After a year, more than half of the hip fracture cases remained restricted regarding housework, gardening, and transport. These findings have important implications for rehabilitation therapy. A fracture, regardless of site, had a major impact on a woman's lifestyle and well-being. Most women were restricted in their activities of daily living and suffered loss of confidence and independence. Short-term morbidity was common for all fractures, with varying degrees of prolonged morbidity often extending to at least a year postfracture.

El-Kaissi S, Pasco JA, Henry MJ, Panahi S, Nicholson JG, Nicholson GC, Kotowicz MA. · Department of Clinical & Biomedical Sciences, Barwon Health, The University of Melbourne, P.O. Box 281, 3220 Geelong, Victoria, Australia. · Osteoporos Int. · Pubmed #16082496 No free full text.

Abstract: To determine the relationship between femoral neck geometry and the risk of hip fracture in post-menopausal Caucasian women, we conducted a retrospective study comparing the femoral neck dimensions of 62 hip fracture cases to those of 608 randomly selected controls. Measurements were made from dual-energy X-ray absorptiometry scans (Lunar DPX-L), using the manufacturer's ruler function, and included: hip axis length (HAL), femoral neck axis length (FNAL), femoral neck width (FNW), femoral shaft width (FSW), medial femoral shaft cortical thickness (FSCT(med)), and lateral femoral shaft cortical thickness (FSCT(lat)). The fracture group was older (median age 78.3 years vs 73.8 years), lighter (median weight 59.9 kg vs 64.5 kg), and, after adjustment for age, taller (mean height 158.7+/-0.8 cm vs 156.7+/-0.2 cm) than the controls. Furthermore, bone mineral density was lower in this group (0.682+/-0.016 g/cm(2) vs 0.791+/-0.006 g/cm(2)). After adjustment for age, bone mineral content (BMC) or height, hip fracture patients had greater FNW (up to 6.6%) and FSW (up to 6.3%) than did the controls. Each standard deviation increase in FNW and FSW was associated with a 1.7-fold (95% CI 1.3-2.3) and a 2.4-fold (95% CI 1.8-3.2) increase in the fracture risk, respectively. BMC-adjusted FNAL was greater in the fracture group (+2.1%) than in the controls, while the age-adjusted FSCT(med) was reduced (-7.2%). There was a trend towards longer HAL (up to 2.1%) after adjustment for age or BMC, and thinner age-adjusted FSCT(lat) (-1.7%) in fracture patients that did not reach statistical significance. In multivariate analysis, the risk of hip fracture was predicted by the combination of age, FNW, FSW, BMC and FSCT(med). HAL was not analyzed because of the small number of HAL measurements among fracture cases. We conclude that post-menopausal women with hip fractures have wider femoral necks and shafts, thinner femoral cortices and longer femoral neck axis lengths than do women with no fractures. Alteration in hip geometry is associated with the risk of hip fracture.

Jacka FN, Pasco JA, Henry MJ, Kotowicz MA, Dodd S, Nicholson GC, Berk M. · University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, PO Box 281, Geelong 3220, Victoria, Australia. · Menopause. · Pubmed #15668605 No free full text.

Abstract: OBJECTIVE: Reduced bone mineral density (BMD) in women with a history of depressive disorders has been shown in some, but not all studies. This study investigated the association between self-reported depression and BMD in an age-stratified community sample of perimenopausal women residing in the South-Eastern region of Australia. DESIGN: Symptoms of depression in the year between July 2000 and July 2001 were ascertained by a self-report questionnaire based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Women in the perimenopausal group who had undergone a BMD total hip and spine assessment within the 12-month period after the depression assessment were included in the analysis, resulting in a sample of 78 women aged 45 to 60 years. RESULTS: In this sample, 14 women were identified as depressed. There was no difference in age, hormone therapy (HT) use, or unadjusted BMD at the total hip or spine between the depressed and nondepressed women (P = 0.14, 0.89, 0.57, and 0.70, respectively), but the depressed women tended to be heavier [depressed (median weight, interquartile range = 80 kg, 66-94) vs nondepressed (72 kg, 61-80) P = 0.06]. Whereas there was no significant difference in age-, HT-, and weight-adjusted BMD at the spine [depressed (mean +/- SE = 1.21 +/- 0.05) vs nondepressed (1.28 +/- 0.03 g/cm(2)) P = 0.18], adjusted BMD at the total hip for the depressed women was 7.8% lower than for the nondepressed [depressed (mean +/- SE = 0.957 +/- 0.038) vs nondepressed (1.038 +/- 0.023 g/cm(2)) P = 0.04]. CONCLUSIONS: These results suggest that in perimenopausal women, self-reported depression is associated with lower BMD at the hip.

Henry MJ, Pasco JA, Pocock NA, Nicholson GC, Kotowicz MA. · The University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Geelong, Victoria, Australia. · Australas Radiol. · Pubmed #15601326 No free full text.

Abstract: Bone densitometry reports a measure of fracture risk in comparison with young adults (T-scores) and age-matched peers (Z-scores). To date, each manufacturer has provided its own reference range resulting in lack of uniformity. The Australia and New Zealand Bone and Mineral Society and Osteoporosis Australia have recognized the need to standardize the reference range and have recommended that data generated by the Geelong Osteoporosis Study (GOS) be used Australia-wide. The GOS recruited a random, population-based sample of adult women and measured bone mineral density (BMD) at the proximal femur and spine using a Lunar DPX-L. These data were used to establish reference ranges for Lunar machines and, using conversion equations, for Norland and Hologic machines. The new standardized Australian reference ranges for BMD will enable consistent diagnosis of osteoporosis and categorization of fracture risk across different types of densitometers.

Pasco JA, Kotowicz MA, Henry MJ, Sanders KM, Seeman E, Nicholson GC. · Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, P.O. Box 281, 3220 Geelong, Australia. · Osteoporos Int. · Pubmed #15205713 No free full text.

Abstract: In this population-based study, we evaluated the association between exposure to hormone therapy (HT), bone mineral density (BMD) and the prevalence of non-vertebral fractures. The study was set in a region located in southeastern Australia where complete fracture ascertainment was determined from radiological reports. Current HT use for at least 6 months was ascertained in women with non-vertebral fractures [median age 70.9 years; inter-quartile range (IQR) 66.5-75.9 years] and randomly selected controls (median age 70.8 years; IQR 65.2-75.0 years). Current HT use was documented in 20 of 262 cases and 49 of 364 controls. The odds ratio (OR) for non-vertebral fracture associated with HT use was 0.53 (95% CI 0.31-0.92). HT use was associated with 2.6-7.5% higher BMD at axial and appendicular sites. HT use is associated with a halving of risk for non-vertebral fractures and higher BMD.

Pasco JA, Henry MJ, Kotowicz MA, Sanders KM, Seeman E, Pasco JR, Schneider HG, Nicholson GC. · Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Victoria, Australia. · J Bone Miner Res. · Pubmed #15068498 No free full text.

Abstract: In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures. INTRODUCTION: In a population of women who reside in a temperate climate and do not generally receive dietary vitamin D supplementation, we investigated whether seasonal vitamin D insufficiency is associated with increased risk of fracture. MATERIALS AND METHODS: An observational, cross-sectional, population-based study set in southeastern Australia (latitude 38-39 degrees S). Participants were drawn from a well-defined community of 27,203 women >/=55 years old: 287 randomly selected from electoral rolls, 1635 with incident fractures, and 1358 presenting to a university hospital with falls. The main outcome measures were annual periodicities of ultraviolet radiation, serum 25-hydroxyvitamin D [25(OH)D], serum parathyroid hormone (PTH), serum C-telopeptide (CTx), BMD, falls, and fractures. RESULTS: Cyclic variations in serum 25(OH)D lagged 1 month behind ultraviolet radiation, peaking in summer and dipping in winter (p < 0.001). Periodicity of serum PTH was the inverse of serum 25(OH)D, with a phase shift delay of 1 month (p = 0.004). Peak serum CTx lagged peak serum PTH by 1-2 months. In late winter, a greater proportion of falls resulted in fracture (p < 0.001). Seasonal periodicity in 439 hip and 307 wrist fractures also followed a simple harmonic model (p = 0.078 and 0.002, respectively), peaking 1.5-3 months after the trough in 25(OH)D. CONCLUSIONS: A fall in 25(OH)D in winter is accompanied by increases in (1) PTH levels, (2) bone resorption, (3) the proportion of falls resulting in fracture, and (4) the frequency of hip and wrist fracture. Whether vitamin D supplementation in winter can reduce the population burden of fractures requires further investigation.

Pasco JA, Henry MJ, Sanders KM, Kotowicz MA, Seeman E, Nicholson GC, Anonymous00354. · Department of Clinical and Biomedical Sciences: Barwon Health, The University of Melbourne, Geelong, Australia. · J Bone Miner Res. · Pubmed #14753732 No free full text.

Abstract: This population-based study documented beta-blocker use in 59/569 cases with incident fracture and 112/775 controls. OR for fracture associated with beta-blocker use was 0.68 (95%CI, 0.49-0.96). Beta-blockers were associated with higher BMD at the total hip (2.5%) and UD forearm (3.6%) after adjusting for age, anthropometry, and thiazide use. Beta-blocker use is associated with reduced fracture risk and higher BMD. INTRODUCTION: Animal data suggests that bone formation is under beta-adrenergic control and that beta-blockers stimulate bone formation and/or inhibit bone resorption. MATERIALS AND METHODS: We evaluated the association between beta-blocker use, bone mineral density (BMD), and fracture risk in a population-based study in Geelong, a southeastern Australian city with a single teaching hospital and two radiological centers providing complete fracture ascertainment for the region. Beta-blocker use was documented for 569 women with radiologically confirmed incident fractures and 775 controls without incident fracture. Medication use and lifestyle factors were documented by questionnaire. RESULTS: Odds ratio for fracture associated with beta-blocker use was 0.68 (95% CI, 0.49-0.96) for any fracture. Adjusting for age, weight, medications, and lifestyle factors had little effect on the odds ratio. Beta-blocker use was associated with a higher BMD at the total hip (2.5%, p = 0.03) and ultradistal forearm (3.6%, p = 0.04) after adjustment for age, anthropometry, and thiazide use. CONCLUSION: Beta-blockers are associated with a reduction in fracture risk and higher BMD.

Vaughan T, Pasco JA, Kotowicz MA, Nicholson GC, Morrison NA. · Genomics Research Center, School of Health Science, Gold Coast Campus Griffith University, Queensland, Australia. · J Bone Miner Res. · Pubmed #12162506 No free full text.

Abstract: The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.

Henry MJ, Pasco JA, Seeman E, Nicholson GC, Sanders KM, Kotowicz MA. · The University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, P.O. Box 281, Geelong 3220, Australia. · J Clin Epidemiol. · Pubmed #12160911 No free full text.

Abstract: Osteoporosis, in the absence of fracture, is defined as a deficit in bone mineral density (BMD) of 2.5 SD or more below the young adult reference mean in postmenopausal Caucasian populations. BMD is a measure of fracture risk but not the sole predictor. We have assessed a combination of easily accessible measures of age, height, weight, and BMD to improve fracture risk assessment. Women with low trauma fractures and a control group were recruited from south-eastern Australia. Discriminant analysis derived multivariate equations that assessed fracture risk. Age was not in the best models at the spine and forearm sites. Weight and height contributed to the relationship for the forearm sites only. At the proximal femur, the BMD level that separates fracture cases from nonfracture cases, increases with age. These separation levels of BMD were higher than the WHO's level of osteoporosis (T-score < -2.5 SD) at ages older than 62 years. This increasing BMD threshold with age suggests that other age-related risk factors assume increasing importance among the elderly.

Sanders KM, Nicholson GC, Ugoni AM, Seeman E, Pasco JA, Kotowicz MA. · The University of Melbourne, Department of Clinical and Biomedical Sciences, Barwon Health, Geelong Hospital, Geelong 3220, Australia. · J Epidemiol Community Health. · Pubmed #12011207 links to  free full text

Abstract: BACKGROUND: Urban and rural communities differ in the incidence of several diseases including coronary heart disease and some cancers. Lower hip fracture rates among rural than urban populations have been reported but few studies have compared rural and urban fractures at sites other than the hip. OBJECTIVE: To compare total and site specific fracture rates among adult residents of rural and urban communities within the same population. DESIGN AND SETTING: This is a population based study on osteoporosis in Australia. All fractures occurring in adult residents over a two year period were ascertained using radiological reports. The rural and urban areas are in close proximity, with the same medical, hospital, and radiological facilities permitting uniform fracture ascertainment. MAIN OUTCOME MEASURES: All fracture rates were age adjusted and sex adjusted to the Australian population according to the 1996 census of the Australian Bureau of Statistics and described as the rate per 10 000 person years. The p values refer to the adjusted rate difference. RESULTS: The hip fracture rate (incidence per 10 000 person years) was 32% lower (39 v 57, p<0.001), and the total fracture rate 15% lower (160 v 188, p=0.004) among rural than urban residents, respectively. The lower fracture rates in the rural population were also apparent for pelvic fractures. CONCLUSION: In the older rural population, lower fracture rates at sites typically associated with osteoporosis suggest environmental factors may have a different impact on bone health in this community. If the national rate of hip fracture could be reduced to that of the rural population, the projected increase in hip fracture number attributable to aging of the population could be prevented.

Pasco JA, Kotowicz MA, Henry MJ, Sanders KM, Nicholson GC, Anonymous00112. · Department of Clinical and Biomedical Sciences-Barwon Health, The University of Melbourne, Geelong Hospital, Barwon Health, PO Box 281, Geelong 3220, Australia. · Arch Intern Med. · Pubmed #11871921 links to  free full text

Abstract: BACKGROUND: Recent data suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decrease fracture risk and increase bone mineral density (BMD). METHODS: This cross-sectional study is set in southeastern Australia. We evaluated the association between statin use, fracture risk, and BMD in 1375 women (573 with incident fractures and 802 without incident fracture, all drawn from the same community). Fractures were identified radiologically. Medication use and lifestyle factors were documented by questionnaire. RESULTS: Unadjusted odds ratio for fracture associated with statin use was 0.40 (95% confidence interval [CI], 0.23-0.71). Adjusting for BMD at the femoral neck, spine, and whole body increased the odds ratio to 0.45 (95% CI, 0.25-0.80), 0.42 (95% CI, 0.24-0.75), and 0.43 (95% CI, 0.24-0.78), respectively. Adjusting for age, weight, concurrent medications, and lifestyle factors had no substantial effect on the odds ratio for fracture. Statin use was associated with a 3% greater adjusted BMD at the femoral neck (P =.08), and BMD tended to be greater at the spine and whole body but did not achieve statistical significance. CONCLUSION: The substantial 60% reduction in fracture risk associated with statin use is greater than would be expected from increases in BMD alone.

Henry MJ, Pasco JA, Seeman E, Nicholson GC, Sanders KM, Kotowicz MA, Anonymous00156. · The University of Melbourne, Department of Clinical and Biomedical Sciences, Geelong, Australia. · J Clin Densitom. · Pubmed #11748333 No free full text.

Abstract: Fracture risk is determined by bone mineral density (BMD). The T-score, a measure of fracture risk, is the position of an individual's BMD in relation to a reference range. The aim of this study was to determine the magnitude of change in the T-score when different sampling techniques were used to produce the reference range. Reference ranges were derived from three samples, drawn from the same region: (1) an age-stratified population-based random sample, (2) unselected volunteers, and (3) a selected healthy subset of the population-based sample with no diseases or drugs known to affect bone. T-scores were calculated using the three reference ranges for a cohort of women who had sustained a fracture and as a group had a low mean BMD (ages 35-72 yr; n = 484). For most comparisons, the T-scores for the fracture cohort were more negative using the population reference range. The difference in T-scores reached 1.0 SD. The proportion of the fracture cohort classified as having osteoporosis at the spine was 26, 14, and 23% when the population, volunteer, and healthy reference ranges were applied, respectively. The use of inappropriate reference ranges results in substantial changes to T-scores and may lead to inappropriate management.

Pasco JA, Henry MJ, Nicholson GC, Sanders KM, Kotowicz MA. · The University of Melbourne, Department of Clinical and Biomedical Sciences--Barwon Health, The Geelong Hospital, VIC. · Med J Aust. · Pubmed #11700831 No free full text.

Abstract: OBJECTIVE: To assess vitamin D intake and casual exposure to sunshine in relation to serum 25-hydroxyvitamin D (25OHD) levels. DESIGN: Cross-sectional study of a population-based, random sample of women aged 20-92 years, assessed between 1994 and 1997. SETTING AND PARTICIPANTS: 861 women from the Barwon Statistical Division (population, 218000), which includes the city of Geelong (latitude 38 degrees south) in Victoria. MAIN OUTCOME MEASURES: Vitamin D intake; serum 25OHD level; season of assessment; exposure to sunshine. RESULTS: Median intake of vitamin D was 1.2 microg/day (range, 0.0-11.4 microg/day). Vitamin D supplements, taken by 7.9% of participants, increased intake by 8.1% to 1.3 microg/day (range, 0.0-101.2 microg/day) (P< 0.001). A dose-response relationship in serum 25OHD levels was observed for sunbathing frequency before and after adjusting for age (P< 0.05). During winter (May-October), serum 25OHD levels were dependent on vitamin D intake (partial r2= 0.01; P<0.05) and were lower than during summer (November-April) (age-adjusted mean, 59nmol/L [95% Cl, 57-62] v 81 nmol/L [95% CI, 78-84]; P<0.05). No association was detected between serum 25OHD and vitamin D intake during summer. The prevalences of low concentrations of serum 25OHD were, for <28nmol/L, 7.2% and 11.3% overall and in winter, respectively; and, for <50 nmol/L, 30.0% and 43.2% overall and in winter, respectively. CONCLUSIONS: At latitude 38 degrees south, the contribution of vitamin D from dietary sources appears to be insignificant during summer. However, during winter vitamin D status is influenced by dietary intake. Australia has no recommended dietary intake (RDI) for vitamin D, in the belief that adequate vitamin D can be obtained from solar irradiation alone. Our results suggest that an RDI may be needed.

Doherty DA, Sanders KM, Kotowicz MA, Prince RL. · Department of Medicine, University of Western Australia, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia. · Osteoporos Int. · Pubmed #11305078 No free full text.

Abstract: We examined the incidence of fragility fractures in Australian women 50 years of age and over using a Markov process with Monte Carlo simulations. The lifetime risks and the risks of sustaining first and subsequent clinically diagnosed fractures at osteoporotic sites were estimated according to age, nursing home entry and mortality rates. Hip and spine fractures were evaluated individually and fractures of humerus, forearm, wrist, ribs, pelvis, upper leg (excluding proximal femur) and tibia/fibula were considered in combination. The model predicted that 42.1% of women aged 50 years will sustain at least one fracture in their remaining lifetime, of whom half are expected to sustain multiple fractures. The lifetime risks of sustaining hip, clinical spine and other fractures were 17.0%, 9.6% and 30.4%, with the risks of multiple fractures at these sites estimated at 19.5%, 39.7% and 35.7% respectively. The proportion of women expected to sustain their first fracture increased from 1.9% of the population under 55 years of age up to 49.1% of women over 89 years of age. The 5-year age-specific risks of sustaining any subsequent fractures increased from 2.8% of women under the age of 55 years to 61.6% for women age 89 years and over. The increased risks of new fractures following a first fracture lead to a considerable burden of multiple fractures.

Henry MJ, Pasco JA, Nicholson GC, Seeman E, Kotowicz MA. · Department of Medicine, St.Vincent's Hospital, Victoria, Australia. · J Clin Densitom. · Pubmed #11090233 No free full text.

Abstract: To evaluate the prevalence of osteoporosis at various sites among Australian women, cross-sectional bone mineral density (BMD) data for adult females was obtained from an age-stratified population-based sample (n = 1494; 20-94 yr) drawn at random from the Barwon Statistical Division, a population characteristic of Australia. Age- and weight- (and for three sites, height) matched reference ranges for BMD at the lumbar spine, proximal femur, forearm, and total body were developed using regression techniques. The cutoff BMD level for osteoporosis at the PA spine was 0. 917g/cm(2) and 0.713 g/cm(2) at the femoral neck according to the World Health Organization (WHO) guidelines. The upper cutoff level for osteopenia was 1.128 g/cm(2) at the PA spine and 0.913g/cm(2) for the femoral neck. The proportion of Australian women categorized as having osteoporosis at the PA spine, femoral neck, or midforearm ranged from 0.9% among those aged 40-44 yr to 87.0% for those older than 79 yr. This study provides reference data representative of the Australian female population. A large proportion of elderly Australian women has osteoporosis according to the WHO guidelines.

Pasco JA, Sanders KM, Henry MJ, Nicholson GC, Seeman E, Kotowicz MA. · The University of Melbourne, Department of Medicine, The Geelong Hospital, Vic. · Aust N Z J Med. · Pubmed #10800873 No free full text.

Abstract: BACKGROUND: Dietary calcium deficiency may be a risk factor for osteoporosis. AIMS: To estimate habitual calcium intakes and prevalence of calcium supplementation among free-living Australian women and validate a calcium-specific food-frequency questionnaire. METHODS: Calcium intakes for 1045 randomly selected women (20-92 years) were estimated by questionnaire which was tested against estimates from four day weighed records kept by 32 randomly selected women. RESULTS: The mean difference between calcium estimates was not statistically significantly different from zero (mean difference=121 mg; standard deviation of differences=357 mg; p>0.05). There was moderate agreement (weighted kappa=0.4) between methods in ranking subjects into tertiles of calcium intake. Mean dietary calcium intakes were 615 mg/day for 20-54 years, 646 mg/day for 55-92 years and 782 mg/day for lactating women. Seventy-six per cent of women aged 20-54 years, 87% of older and 82% of lactating women had intakes below the recommended dietary intake (RDI). There was no association detected between calcium intake and age. Dairy foods provided 79.0% of dietary calcium intake. Calcium supplements were used by 6.6% and multivitamins by a further 4.3% of women. Supplementation was independent of dietary calcium intake and more likely used by postmenopausal women. CONCLUSIONS: Our results suggest that 76% of women consume less than the RDI even when supplemental calcium is included. Furthermore, 14% have less than the minimal requirement of 300 mg/day and would, therefore, be in negative calcium balance and at risk of bone loss. Despite advertising campaigns promoting better nutrition and increased awareness of osteoporosis, many women are failing to achieve an adequate calcium intake.