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M A Kotowicz

Publications and source records attributed to M A Kotowicz.

34 records · Page 2Linked to original sources

Health burden of hip and other fractures in Australia beyond 2000. Projections based on the Geelong Osteoporosis Study.

OBJECTIVE: To calculate the expected increase in the number of fractures in adults attributable to the predicted increase in the number of elderly Australians. DATA SOURCES: All fractures in adult residents (> or = 35 years) of the Barwon Statistical Division (total population, 218,000) were identified from radiological reports from February 1994 to February 1996. The Australian Bureau of Statistics supplied predictions of Australia's population (1996 to 2051). MAIN OUTCOME MEASURE: The projected annual number of fractures in Australian adults up to 2051 (based on stable rates of fracture in each age group). RESULTS: The number of fractures per year is projected to increase 25% from 1996 to 2006 (from 83,000 fractures to 104,000). Hip fractures are projected to increase 36% (from 15,000 to 21,000) because of a substantial rise in the number of elderly aged 85 years and over. Hip fractures are expected to double by 2026 and increase fourfold by 2051. CONCLUSIONS: In contrast to Europe and North America, where numbers of hip fractures are expected to double by 2026 and then stabilise, in Australia hip fractures will continue to place a growing demand on healthcare resources for many decades. These projections can be used for setting goals and evaluating the costs and benefits of interventions in Australia.

Adult↗

Femoral neck dimensions are unlikely to be associated with age at menarche.

Hip axis length (HAL) has been reported as an independent risk factor for hip fracture. Later puberty may increase bone size because of delayed epiphyseal fusion. We sought to identify associations between bone size at the proximal femur with age at menarche and other indices of growth such as stature. Femoral neck dimensions were measured from dual-energy X-ray absorptiometry scans of the proximal femur in a random sample of 203 premenopausal Caucasian women (age 20-30 years). There were no associations between age at menarche and HAL, femoral axis length (FAL) or femoral neck width (FNW). Age at menarche was associated with height (r = 0.2, p = 0.02). Variations in HAL, FAL and FNW do not appear to be related to age at menarche.

Absorptiometry, Photon↗

Age- and gender-specific rate of fractures in Australia: a population-based study.

There is little population-based data concerning fracture rates in Australia. We ascertained all fractures occurring during 2 years in adults aged 35 years and over residing within a defined region (population 218 000), representative of the Australian population. The major strength of this study is the comprehensive ascertainment of fractures, which was ensured by regular searches of the only two radiologic providers in the Geelong Osteoporosis Study region. Nevertheless, vertebral fractures are likely to be underestimated since our ascertainment relied on a clinical indication for a medical imaging procedure. Among those aged 35-55 years, the fracture rate (persons per 10,000/year) in men was about double the rate in women (65 vs 35). The fracture rate was almost 7 times higher in women over 60 years versus women less than 55 years of age. In contrast, the fracture rate in men over 60 years was only 50% higher than in men less than 55 years of age (72 vs 104). Fracture rates in women and men were highest at the hip (28 and 10 respectively), spine (21 and 7), distal forearm (Colles') (18 and 4) and humerus (11 and 3), and were 3-4 times higher in women than men. These fractures accounted for 63% of all fractures in women and 32% in men. By contrast, the rate of lower leg and ankle fractures was less than 10 per 10,000 in both women and men and did not increase to the same extent with age. Hip fracture rates appear high, particularly among the older age strata, compared with retrospective ascertainment in other populations. In Australia, as in many other countries, there is an increasing longevity of the population. The number of women aged 90 years and over increased by 32% and the number of men of this age increased by 48% in the 5 years between the Australian national census of 1991 and 1996. Given stable fracture rates, the substantial health burden imposed by age-related fractures, particularly hip fractures, will continue to escalate in both women and men.

Adult↗

Identification of incident fractures: the Geelong Osteoporosis Study.

BACKGROUND: Complete fracture ascertainment is critical for fracture cost estimates and planning for future health care facilities. Virtually complete ascertainment is possible for hip fractures because they nearly always require hospitalisation. AIMS: To validate the use of radiological reports as a resource for ascertaining fracture cases, using hip fracture as a model. METHODS: Hip fracture rates obtained from radiological reports were compared with rates obtained from hospital discharge summaries of medical records using International Classification of Diseases-9 (ICD-9) codes 820.0-820.9 and 733.1 over a three-year period. RESULTS: Hip fracture cases numbered 589 using radiological reports and 585 using medical records. Discharge summaries failed to identify 15 cases ascertained through radiology reports whereas 11 cases ascertained through medical records were not identified from X-ray reports. The age-specific incidence rates for radiological ascertainment were within the 95% confidence limits of the rates derived from medical records. CONCLUSIONS: Among a population of patients generally admitted to hospital for treatment of their fracture, we were able to identify more cases from radiological reports than from medical records. Incidence rates for hip fracture were comparable using the two methods. Radiological reports provide a valuable resource for identifying incident fractures. This method of case ascertainment would be suitable for identifying both major and minor fractures in regions with self-contained health services where access to all radiological reports is possible.

Adolescent↗

Gemfibrozil treatment increases low-density lipoprotein particle size in Type 2 diabetes mellitus but does not alter in vitro oxidizability.

The aim of this study was to determine the effect of the lipid modifying agent gemfibrozil on lipid and coagulation risk factors in patients with Type 2 diabetes mellitus (Type 2 DM). Twenty-six subjects with Type 2 DM and dyslipidaemia were treated for 24 weeks with either gemfibrozil 600 mg orally twice daily or placebo in a double-blind randomized trial. Lipid profiles, fibrinogen, Factor VII, and plasminogen activator inhibitor-1 (PAI-1) were measured by routine laboratory methods. Low density lipoprotein (LDL) size was determined by gradient gel electrophoresis and the resistance of LDL to copper-induced oxidation was assessed by measuring absorbance at 234 nm. Gemfibrozil significantly reduced total cholesterol (-0.9 (-0.48, -1.32) mmol l(-1); p < 0.05) and triglycerides (-2.7 (-1.55, -1.35) mmol l(-1); p < 0.001) vs placebo. The fall in triglyceride was reflected by a fall in VLDL cholesterol levels in the gemfibrozil treated group vs placebo (-1.31 mmol l(-1); p < 0.001). LDL-cholesterol level did not change but LDL particle size increased by 0.5 nm (0.01, 0.93); P < 0.02. The increase in particle size was inversely correlated with the change of triglyceride level (r = -0.79, p < 0.0001) but did not result in any reduction of susceptibility to copper-induced oxidation. There were no significant changes in the coagulation parameters studied. Because of its ability to correct the lipid abnormalities associated with Type 2 DM particularly hypertriglyceridaemia, gemfibrozil provides a useful therapeutic option in the management of diabetic dyslipidaemia but it does not alter in vitro oxidizability of LDL.

Blood Coagulation↗

The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study.

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either "low" or "high" trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual-energy X-ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean +/- SEM) were reduced in both the low and high trauma groups, respectively: spine-posterior-anterior (-0.50 +/- 0.05 and -0.21 +/- 0.08), spine-lateral (-0.28 +/- 0.06 and -0.19 +/- 0.10), femoral neck (-0.42 +/- 0.04 and -0.26 +/- 0.09), Ward's triangle (-0.44 +/- 0.04 and -0.28 +/- 0.08), trochanter (-0.44 +/- 0.05 and -0.32 +/- 0.08), total body (-0.46 +/- 0.06 and -0.32 +/- 0.08), ultradistal radius (-0.47 +/- 0.05 and -0.42 +/- 0.07), and midradius (-0.52 +/- 0.06 and -0.33 +/- 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age-adjusted odds ratio for osteoporosis (t-score < -2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

Absorptiometry, Photon↗

Relationship of serum leptin to total and truncal body fat.

1. In this study we investigated the relationship between serum leptin levels and body fat distribution in a random sample of women of widely ranging age and body mass index. Anthropometry and dual energy X-ray absorptiometry were used to measure body fat and its distribution. 2. Leptin levels (log transformed) were not significantly correlated with age, but were significantly positively correlated (P < 0.001) with most anthropometric measures except waist-to-hip circumference ratio. The strongest correlations were with total grams of body fat and percentage body fat (r = 0.68 and 0.76 respectively, P < 0.001). When corrected for percentage body fat the partial correlation coefficients for all other measures became non-significant. The correlation with truncal body fat fell significantly from 0.66 to -0.05 after correction, but the partial correlation with total body fat remained significant (P < 0.005) when grams of truncal fat were controlled for (r = 0.21). 3. These results indicate that the relationship of serum leptin to percentage body fat is the strongest, and that truncal body fat, although the most metabolically active, does not appear to have an independent association with serum leptin.

Absorptiometry, Photon↗

Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: a randomized, placebo-controlled trial.

PURPOSE: The potent bisphosphonates offer great promise in the management of Paget's disease of bone, but are currently available only as parenteral preparations in most countries. There is a need for a well-tolerated, oral therapy. Furthermore, none of the currently available therapies have been rigorously demonstrated to heal the lytic bone lesions characteristic of this condition. Alendronate is a potent new oral aminobisphosphonate that has shown promising effects on Paget's disease in preliminary studies. METHODS: We report a double-blind, randomized comparison of oral alendronate 40 mg/day and placebo over 6 months in 55 patients with Paget's disease. Efficacy was determined from measurements of biochemical indices of bone turnover (serum alkaline phosphatase and urine N-telopeptide) and blinded radiologic assessment of lytic bone lesions. RESULTS: N-telopeptide excretion declined by 86% and serum alkaline phosphatase by 73% in patients receiving alendronate, but remained stable in patients receiving placebo (P < 0.001 between groups for both indices). Responses were similar whether or not patients had previously received bisphosphonate treatment. Alendronate treatment normalized alkaline phosphatase in 48% of patients. Forty-eight percent of alendronate-treated patients showed radiologic improvement in osteolysis whereas in the placebo group only 4% improved (P = 0.02 for between-groups comparison). No patient in either group showed worsening of osteolysis. Bone histomorphometry indicated that alendronate tended to normalize turnover indices. There was no evidence of abnormal mineralization in bone biopsies taken from 12 alendronate-treated subjects. The treatment was well tolerated. CONCLUSION: Oral alendronate appears to be a safe and effective therapy for Paget's disease and results in healing of lytic bone lesions.

Administration, Oral↗

Risk of hip fracture in women with vertebral fracture.

In a population-based retrospective cohort study, Rochester women aged 35-69 years who were first diagnosed with one or more vertebral fractures in 1950-1979 were followed for the development of a subsequent hip fracture. The 336 women with no history of hip fracture at the time of their vertebral fracture experienced 52 proximal femur fractures in 4788 person-years of follow-up. The standardized morbidity ratio (SMR) of observed to expected hip fractures was 1.8 (95% CI, 1.3-2.4) and was higher for intertrochanteric than cervical femoral fractures (SMR, 2.3 versus 1.3; P = 0.07). Hip fracture risk among women with symptomatic vertebral fractures was slightly less than in those with asymptomatic vertebral fractures (SMR, 1.8 versus 2.3; not significant), and younger women had no higher risk of a subsequent hip fracture than women who were > or = 60 years of age at the time of their vertebral fracture (SMR, 1.4 versus 1.8; not significant). Alternative explanations are possible, but these data are consistent with heterogeneity in the pathogenesis of different osteoporotic fractures.

Adult↗

Treatment of postmenopausal osteoporosis with transdermal estrogen.

OBJECTIVE: To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures. DESIGN: Double-blind, randomized, placebo-controlled clinical trial lasting 1 year. SETTING: Referral-based outpatient clinic. PATIENTS: Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis. INTERVENTIONS: Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo. MEASUREMENTS: Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate. RESULTS: Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2; P = 0.007), femoral trochanter (7.6 compared with 2.1; P = 0.03), and midradius (1.0 compared with -2.6, P less than 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4; P = 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, -0.35 compared with 0.02 nmol/L; P less than 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, -12.9 compared with -6.2% per year; P = 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% CI, 0.16 to 0.95). CONCLUSIONS: Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.

Administration, Cutaneous↗

Relationship of glucocorticoid dosage to serum bone Gla-protein concentration in patients with rheumatologic disorders.

Serum bone Gla-protein (BGP) measurements in 50 rheumatic disease patients receiving long-term prednisone therapy revealed an inverse relationship (r = -0.71, P less than 0.001) between serum BGP levels and prednisone dosage. Multiple regression analysis demonstrated significant relationships (R2 = 0.72, P less than 0.001) between serum BGP1/2 and prednisone dosage, dosage2, serum creatinine, age, and an age-creatinine interaction. This model predicts the suppression of serum BGP with low dosages of steroids and 50% suppression with dosages of 20-25 mg/day.

Adolescent↗

Effect of age on variables relating to calcium and phosphorus metabolism in women.

Lack of adequate data concerning the effect of age on biochemical variables relating to bone and mineral metabolism hampers research on age-related bone loss in women. Furthermore, to detect disease and to monitor therapy, clinical laboratories require reference values derived from an appropriate population sample. Therefore, we determined the age-specific distribution of values for serum concentrations of calcium, inorganic phosphorus, alkaline phosphatase, bone Gla protein, and parathyroid hormone; for creatinine clearance; for fasting urinary calcium:creatinine ratio; and for 24 h urinary excretion of calcium, hydroxyproline, and cyclic AMP in a population-based sample of 301 white women. From this sample, a healthy subgroup of 181 women was identified by medical record review. Age-related effects were seen in all variables except serum calcium and phosphorus. Moreover, substantial differences between the population sample and the healthy subgroup were noted in values for creatinine clearance, serum alkaline phosphatase, and 24 h urinary calcium excretion. These observations may prove useful for assessment of normality in other populations of aging white women.

Adult↗

Relationship between serum intact parathyroid hormone concentrations and bone remodeling in type I osteoporosis: evidence that skeletal sensitivity is increased.

To define the role of parathyroid gland function in the pathophysiology of bone loss in type I (postmenopausal) osteoporosis, we measured serum intact parathyroid hormone (PTH) concentration by immunoradiometric assay (IRMA) and by multisite immunochemiluminometric assay (ICMA) in 63 postmenopausal osteoporotic women (PMOp) with vertebral compression fractures and in 75 age-comparable postmenopausal normal women (PMNl). Also, tetracycline-based histomorphometric indices in cancellous bone were assessed in iliac biopsy samples from 61 PMOp and 28 PMNl women. Serum PTH concentrations by IRMA were similar in PMOp and PMNl (medians, 3.92 and 3.77 pmol/l; NS) but were significantly lower in PMOp by the more sensitive ICMA (medians, 2.82 and 3.14 pmol/l; P less than 0.01). By multiple linear regression analysis, serum PTH was directly related (P less than 0.001) to activation frequency, bone resorption rate, bone formation rate, and the calculated rate of bone loss. For each unit (pmol/l) increase in serum PTH by ICMA, activation frequency increased by 1.3%/year more (P = 0.01), bone resorption rate increased by 3.9%/year more (P = 0.003), and the rate of cancellous bone loss was 2.8% greater (P = 0.0003) in the PMOp women compared with the PMNl women. Concentrations of serum estradiol, but not serum estrone, had a weak opposing effect to PTH, especially for bone formation rate. These data suggest that in PMOp the bone has increased sensitivity to the biologic effects of PTH. This may represent one of the fundamental pathophysiologic defects in PMOp and, in the setting of estrogen deficiency, may explain, in part, their greater rate of bone loss.

Aged↗

Factors influencing reticulophagocytic function in insulin-treated diabetes.

The splenic component of reticulophagocytic function (RPF) was examined in 29 insulin-treated diabetic subjects (13 type I and 16 type II) by measurement of clearance of altered, radiolabeled, autologous erythrocytes. Double-isotope studies were performed with cells altered by: (1) preincubation with N-ethylmaleimide (NEM) and (2) coating with IgG antibody to the Rhesus (Rh) D antigen, labeled with 99mTc and 51Cr, respectively. HLA typing for the A, B, and DR loci was performed in those patients showing a defect in the clearance of IgG-coated cells. Values for half-life (t1/2) were correlated with the incidence of diabetic complications, levels of HbA1, and circulating immune complexes (CIC). Two patterns of abnormal clearance were observed: first, an isolated defect of IgG-coated cell clearance in 7 patients (3 had the HLA B8/DR3 haplotype) and second, abnormal removal of both types of cell in a further 7 patients (3 had B8/DR3). There was no correlation between half-lives as measured by the two methods, although exclusion of the patients with a defect of IgG-coated cell clearance alone yielded a highly significant correlation for the remaining 15 Rh-positive patients (P less than 0.01). Abnormalities of IgG-coated cell clearance were more frequent in patients with HbA1 greater than 9% (P less than 0.02), while t1/2 of NEM-altered cells was significantly greater in patients with CIC (P less than 0.05). There was no correlation between t1/2 and the incidence of peripheral complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Metabolic profiles in diabetic subjects treated with human insulin (Novo) and porcine insulin.

Twenty-four-hour metabolic profiles were used to compare the efficacy of twice-daily injections of purified porcine and human Actrapid and Monotard insulins (Novo) in six insulin-treated diabetic subjects. Although both insulin regimens resulted in similar plasma glucose profiles, values were lower during the night with porcine insulin treatment. These differences in plasma glucose response may represent an increased effectiveness of porcine insulin. Alternatively, evaluation of the plasma glucose profiles by the mean of the daily differences suggests that inherent day-to-day variations in diabetic control could explain the differences observed. Also, the potency of the porcine insulin used was greater than that of the human insulin and may have contributed to the differences in glucose response. No differences were observed in pyruvate, lactate, total ketones, and insulin profiles over the 24-h period. No adverse reactions to human insulin occurred.

Adult↗