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Biomedical subjects

P Sambrook

Publications and source records attributed to P Sambrook.

At least 19 recordsLinked to original sources
PubMed2005

Effect of antiepileptic medication on bone mineral measures.

OBJECTIVE: Long-term antiepileptic drug (AED) use has been associated with bone disease, but many previous studies have been limited by inadequate control subjects. We used a cotwin affected sib-pair model to investigate this issue. METHODS: The authors studied 31 female twin (15 monozygous and 16 dizygous) and four sibling pairs (< 3 years age difference) aged 21 to 75 years, in which one member had > 12 months of AED treatment. Areal bone mineral density (ABMD, g/cm2) was measured at the lumbar spine (LS), total hip (TH), femoral neck (FN), and total forearm (FA). Three primary a priori defined subgroups were analyzed: a) use for > 2 years, b) use of enzyme-inducing AEDs, or c) age older than 40 years. RESULTS: For all pairs (n = 35), there were no significant within-pair differences in any ABMD measure. However, in Subgroup a (n = 27), there was a within-pair difference at the FA (0.513 vs 0.534, -3.9%, p = 0.016). In Subgroup b (n = 29), there was also a within-pair difference at the FA for AED user vs nonuser (0.508 vs 0.529, -3.8%, p = 0.010). In Subgroup c (n = 15), there were within-pair differences at the FA (0.492 vs 0.524, -6.1%, p = 0.017) and the LS (0.884 vs 0.980, -9.8%, p = 0.036). CONCLUSIONS: Patients using AEDs for > 2 years, in particular those taking enzyme-inducing AEDs and those older than 40 years, have significantly lower bone mineral density at clinically relevant fracture risk sites.

Adult↗
PubMed2005

Editorial.

Explore the source record for details and available documents.

Aged↗
PubMed2002

Comparison of genome screens for two independent cohorts provides replication of suggestive linkage of bone mineral density to 3p21 and 1p36.

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Studies of BMD in families and twins have shown that this trait is under strong genetic control. To identify regions of the genome that contain quantitative trait loci (QTL) for BMD, we performed independent genomewide screens, using two complementary study designs. We analyzed unselected nonidentical twin pairs (1,094 pedigrees) and highly selected, extremely discordant or concordant (EDAC) sib pairs (254 pedigrees). Nonparametric multipoint linkage (NPL) analyses were undertaken for lumbar spine and total-hip BMD in both cohorts and for whole-body BMD in the unselected twin pairs. The maximum evidence of linkage in the unselected twins (spine BMD, LOD 2.7) and the EDAC pedigrees (spine BMD, LOD 2.1) was observed at chromosome 3p21 (76 cM and 69 cM, respectively). These combined data indicate the presence, in this region, of a gene that regulates BMD. Furthermore, evidence of linkage in the twin cohort (whole-body BMD; LOD 2.4) at chromosome 1p36 (17 cM) supports previous findings of suggestive linkage to BMD in the region. Weaker evidence of linkage (LOD 1.0-2.3) in either cohort, but not both, indicates the locality of additional QTLs. These studies validate the use, in linkage analysis, of large cohorts of unselected twins phenotyped for multiple traits, and they highlight the importance of conducting genome scans in replicate populations as a prelude to positional cloning and gene discovery.

Adolescent↗
PubMed2001

Selective matrix metalloproteinase (MMP) inhibition in rheumatoid arthritis--targetting gelatinase A activation.

The matrix metalloproteinases (MMP) are a large group of enzymes responsible for matrix degradation. They contribute to joint destruction in rheumatoid arthritis (RA) by directly degrading the cartilage and bone and indirectly promoting angiogenesis (formation of new blood vessels). Inhibition of MMPs is a primary therapeutic target in RA. However, the results of limited clinical trials performed to date are disappointing. Improvements in therapeutic benefit may be achieved by targetting specific MMPs. A subclass of the MMPs, the gelatinases, contribute directly to joint destruction as well as being vital during angiogenesis. Gelatinase A is released as a latent enzyme and must be activated to degrade the matrix. It has a unique mechanism of activation on the cell surface involving membrane-type MMP (MT-MMP). Recently, the serine protease, activated protein C (APC), has been shown to directly activate gelatinase A, without requiring MT-MMP Inhibition of APC represents a selective approach to prevent gelatinase A activation and may prove to be of therapeutic benefit in RA.

Arthritis, Rheumatoid↗
PubMed2001

The incidence of hip fracture in four Asian countries: the Asian Osteoporosis Study (AOS).

The Asian Osteoporosis Study (AOS) is the first multicenter study to document and compare the incidence of hip fracture in four Asian countries. Hosital discharge data for the year 1997 were obtained for the Hong Kong SAR, Singapore, Malaysia and Thailand (Chiang Mai). The number of patients who were 50 years of age and older and who were discharged with a diagnosis of hip fracture (ICD9 820) was enumerated. The age-specific incidence rates were deduced and were directly adjusted to the US white population in 1989. The age-adjusted rates for men and women (per 100,000) are as follows: Hong Kong, 180 and 459; Singapore, 164 and 442; Malaysia, 88 and 218; Thailand, 114 and 289; compared with US White rates of 187 in men and 535 in women, published in 1989. We conclude that there is moderate variation in the incidence of hip fracture among Asian countries. The rates were highest in urbanized countries. With rapid economic development in Asia, hip fracture will prove to be a major public health challenge.

Aged↗
PubMed2001

Corticosteroid osteoporosis.

Corticosteroids are widely used and effective agents for the control of many inflammatory diseases, but corticosteroid osteoporosis is a common problem associated with their long term high dose use. Prevention of corticosteroid osteoporosis is preferable to treatment of established corticosteroid bone loss. Several large double-blind controlled clinical trials in patients with corticosteroid osteoporosis have recently been published that provide new insights into its treatment. Based upon available evidence, the rank order of choice for prophylaxis would be a bisphosphonate followed by a vitamin D metabolite or an oestrogen type medication. Calcium alone appears to be unable to prevent rapid bone loss in patients starting corticosteroids, especially with prednisolone doses at 10 mg a day or greater. If an active vitamin D metabolite is used, calcium supplementation should be avoided unless dietary calcium intake is low. Hormone replacement therapy should be considered if hypogonadism is present. Since vertebral fracture is a common and important complication of high dose corticosteroid therapy, these findings suggest that rapid bone loss and hence fractures, can be prevented by prophylactic treatment. Although the follow-up data is limited, it is likely that such therapy needs to be continued beyond 12 months whilst patients continue significant doses of corticosteroid therapy.

Fractures, Bone↗
PubMed2001

Continuing education: the 1998 Survey of the Royal Australasian College of Dental Surgeons.

BACKGROUND: Continuing education (CE) is an essential professional activity. In the last decade, CE has been actively pursued by the medical profession in Australia and abroad. However, the uptake of CE in dentistry has been much slower and there is minimal Australian data on dental CE. METHODS: To determine the level of CE activity, in 1998, postal questionnaires were sent to all fellows of the Royal Australasian College of Dental Surgeons. The responses were analysed. RESULTS: There was a high response rate (90 per cent) but a moderate usable rate (54 per cent). The results show a biphasic distribution between high and low CE activity. The average amount of activity of those involved in CE was 116 hours per year, above the usually accepted minimum of 100 hours/year. Some groups, particularly members of the specialist divisions of oral and maxillofacial surgeons (215 hours) and periodontists (205 hours), have high levels of CE. However, approximately 25 per cent of college fellows reported little or no CE activity. The survey revealed that inactive fellows are more likely to be older and in general practice. Inactive fellows were also tardy in replying to the questionnaire. CONCLUSION: The high activity CE group needs to be recognised and encouraged to continue. Specific plans to help the low CE activity group should be developed. Although these findings relate directly to the Royal Australasian College of Dental Surgeons, they are presented as they have implications for the dental profession at large.

Age Factors↗
PubMed2001

Protective effect of short-tem calcitriol or cyclical etidronate on bone loss after cardiac or lung transplantation.

Bone loss is most rapid in the immediate period after cardiac or lung transplantation. This randomized study compared the efficacy of 6 months of treatment with either calcitriol (1,25-dihydroxyvitamin D3; 0.5 microg/day) or two cycles of etidronate plus calcium in preventing bone loss in 41 patients undergoing cardiac or lung transplantation. Patients were followed for 18 months after cessation of treatment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). There were no significant differences between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporin over the 2 years. Bone loss did not differ between groups after 6 months and, despite 6 months prophylaxis with either agent, bone loss was significant in both groups at 6 months and 12 months. However, compared with an untreated reference group, both therapies offered significant protection at 6 months and etidronate provided significant protective carryover after therapy had been discontinued. These data suggest short-term prophylaxis with calcitriol or cyclical etidronate is partially effective in reducing bone loss after cardiac or lung transplantation but treatment needs to be continued for a longer term.

Adrenal Cortex Hormones↗
PubMed2001

Risk factors for hip fracture in Asian men and women: the Asian osteoporosis study.

The objectives of the Asian Osteoporosis Study (AOS) were to determine risk factors for hip fracture in men and women in four Asian countries, that is, Singapore, Malaysia, Thailand, and the Philippines. A total of 451 men and 725 women (aged 50 years and over) with hip fractures were compared with an equal number of community controls. A standardized questionnaire was administered by interview. The following relative risks (RRs) were found in women and men by multiple logistic regression: dietary calcium intake < 498 mg/day, 2.0 for women (95% CI, 1.5-2.8) and 1.5 for men (95% CI, 1.0-2.2); no load bearing activity in the immediate past, 2.0 for women (95% CI, 1.4-2.7) and 3.4 for men (95% CI, 2.3-5.1); no vigorous sport activities in young adulthood, 7.2 for women (95% CI, 4.0-13.0) and 2.4 for men (95% CI, 1.6-3.6); cigarette smoking, 1.5 for men (95% CI, 1.0-2.1); alcohol consumption 7 days a week, 2.9 for women (95% CI, 1.0-8.6) and 1.9 for men (95% CI, 1.1-3.2); fell twice or more in the last 12 months, 3.0 for women (95% CI, 1.8-4.8) and 3.4 for men (95% CI, 1.8-6.6); a history of fractures after 50 years of age, 1.8 for women (95% CI, 1.1-2.9) and 3.0 for men (95% CI, 1.6-5.6); a history of stroke, 3.8 for women (95% CI, 2.0-7.1) and 3.6 for men (95% CI, 1.8-7.1); use of sedatives, 2.5 for women (95% CI, 1.0-6.3) and 3.0 for men (95% CI, 1.0-9.7); and use of thyroid drugs, 7.1 for women (95% CI, 2.0-25.9) and 11.8 for men (95% CI, 1.3-106.0). Women who were 1.56 m or taller had an RR of 2.0 (95% CI, 1.3-3.0) for hip fracture and men who were 1.69 m or taller had an RR of 1.9 (95% CI, 1.2-3.1) for hip fracture. Based on these findings, primary preventive programs for hip fracture could be planned in Asia.

Aged↗
PubMed2001

Osteoporosis with low dose corticosteroids: contribution of underlying disease effects and discriminatory ability of ultrasound versus bone densitometry.

OBJECTIVE: Corticosteroid use is associated with rapid bone loss, but the effect of low dose corticosteroids (CS) remains controversial and the extent to which increased fracture risk relates to quantitative effects, as reflected by change in bone mineral density (BMD), or to qualitative effects due to altered microarchitecture is unclear. Moreover the contribution of the underlying disease, for which CS are used, confounds the assessment of CS effects on bone. Our aim was to examine these effects of CS on bone. METHODS: We measured BMD, quantitative ultrasound (US), and clinical and radiological disease indices in 76 patients with rheumatoid arthritis (RA) treated with or without low dose CS. Disease effects were quantitated using the Health Assessment Questionnaire and radiological scores. RESULTS: BMD and US measures were significantly reduced in RA patients compared to age matched controls. Low dose CS use was associated with a further small but nonsignificant reduction in BMD, and US measures did not further discriminate CS effects on bone. Radiological score was an independent predictor of US measures, suggesting that in RA, calcaneal bone may reflect both systemic and local disease effects. CONCLUSION: US did not appear to discriminate effects of low dose CS on bone better than BMD. However, underlying RA disease effects on bone are detectable by US. Quantitative US should be investigated for its utility in assessing disease activity or progress in RA.

Absorptiometry, Photon↗
PubMed2001

Men and osteoporosis.

BACKGROUND: While strict criteria have been developed for defining osteoporosis in women (bone mineral density measurements more than 2.5 standard deviations below the mean for young adult normal women, i.e. t-score value < -2.5), there still remains a controversy regarding the definition in men. Spinal fractures occur in 5% and hip fractures in 6% of men older than 50 years. There are significant differences between men and women with respect to the pathogenesis of osteoporosis, underlying medical conditions and postfracture sequelae. OBJECTIVE: To provide an overview of the pathogenesis, diagnosis and prevention of osteoporosis in men. DISCUSSION: Osteoporosis is increasingly recognised. Data from the Dubbo Osteoporosis Epidemiology Study suggests that 30% of men in Australia aged over 60 years will suffer from an osteoporotic fracture. It is estimated that 30-60% of men presenting with spinal fractures will have another illness contributing to their bone loss. Osteoporotic fractures in men are associated with higher morbidity and mortality than in women. Lifestyle changes together with daily calcium supplementation should be implemented and vitamin D3 should be considered in men with osteopenia.

Bone Density↗
PubMed2001

Guidelines for treatment of osteoporosis in men.

BACKGROUND: Osteoporosis is associated with significant morbidity and mortality in men. Published randomised controlled trials assessing the benefits of therapy in men with osteoporosis are limited, but those available need to be used to develop management guidelines. OBJECTIVE: To present evidence based guidelines for the treatment of osteoporosis in men. DISCUSSION: It is estimated that 30-60% of men presenting with spinal fractures have another illness contributing to their bone disease. Therefore assessment and treatment of coexisting medical conditions is a vital part of management of osteoporosis. While primary prevention of fractures remains crucial, treatment to ensure further fractures do not occur is equally important. Alendronate is the treatment of choice for men with osteoporosis and fractures, with cyclical etidronate an appropriate alternative and testosterone replacement therapy is indicated in hypogonadal men presenting with osteoporosis.

Calcitriol↗
PubMed2000

Antibiotic prescribing practices by South Australian general dental practitioners.

The prescribing habits of a randomly selected approximately 10 per cent sample of South Australian general dental practitioners were obtained by postal questionnaire. Sixty-eight (61 per cent) usable replies were received and analysed. Generally, there was an appropriate level of knowledge of antibiotic prescription. However, there was a tendency toward over-prescription and a demonstrated lack of knowledge of the incidence of adverse reactions, development of multiresistant strains and prophylaxis against bacterial endocarditis. All of these areas are real challenges to the profession, whether in an overall global community health sense or in a highly individualized clinical or medico-legal sense. These issues are discussed and the profession is urged to reconsider and re-educate itself on these challenges.

Anti-Bacterial Agents↗
PubMed2000

Alendronate in early postmenopausal women: effects on bone mass during long-term treatment and after withdrawal. Alendronate Osteoporosis Prevention Study Group.

We studied the effect on bone mass of alendronate treatment for 5 yr and its withdrawal. Four hundred and forty-seven postmenopausal women with normal bone mass entered a 3-yr randomized trial followed by a 2-yr open label extension. Three hundred and eleven women completed the first 3 yr, and 263 consented to continue and completed the extension. We are reporting data from groups using the dose of alendronate currently approved for osteoporosis prevention (5 mg) or from the group in which alendronate treatment was withdrawn: 52 women received alendronate (5 mg) for 5 yr (group I), 56 received 3 yr of placebo followed by alendronate (5 mg) for 2 yr (group II), and 52 received alendronate (20 mg) for 2 yr followed by 3 yr off therapy (group III). In group I, alendronate (5 mg) increased bone mineral density (BMD) at the spine and trochanter by 2.5-3.2% (P < 0.001 vs. baseline) and stabilized total body and femoral neck BMD (change vs. baseline, P = NS) over 5 yr. By the end of 5 yr, BMD was comparable at the spine, hip, and total body in groups I and III. The 3-yr decrease in BMD after withdrawal of alendronate (20 mg) in group III was 1.8-5.7% (P < 0.01 vs. baseline) and similar to the 3-yr decrease in BMD in group II during the initial 3 yr. In conclusion, alendronate (5 mg) for 5 yr or alendronate (20 mg) for 2 yr followed by 3 yr off therapy prevented postmenopausal bone loss. After withdrawal of alendronate (20 mg), bone loss resumed at the normal early postmenopausal rate.

Absorptiometry, Photon↗
PubMed2000

Effect of calcitriol on bone loss after cardiac or lung transplantation.

Rapid bone loss after cardiac and lung transplantation results in an increased risk of osteoporotic fracture. This study examined the efficacy of treatment with calcitriol (1,25-dihydroxyvitamin D3) in preventing bone loss in patients undergoing cardiac or lung transplantation. In this 2-year double-blind, stratified study, 65 patients undergoing cardiac or single lung transplantation were randomly allocated to receive either placebo or calcitriol (0.5-0.75 microg/day), the latter for either 12 months or 24 months. All patients received 600 mg calcium/day. Bone mineral density (BMD) was measured every 6 months for 2 years by dual-energy X-ray absorptiometry. There was no significant difference between groups with respect to age or cumulative dose of prednis(ol)one or cyclosporine over the 2 years. Bone loss at the proximal femur was significantly reduced or prevented at all three sites by treatment with calcitriol for 2 years compared with treatment with calcium alone. Treatment with calcitriol for 12 months followed by calcium for 12 months resulted in similar proximal femoral bone loss to that seen in those patients treated with calcium for 24 months, suggesting calcitriol prophylaxis needs to be continued beyond 12 months. At the lumbar spine, there were no significant differences in BMD between groups. Over a period of 2 years, 22 new vertebral fractures/deformities occurred in 4 patients treated with calcium alone compared with one new vertebral fracture in 1 patient treated with calcitriol. Because the sample size was too low to provide reliable interpretation of vertebral fracture rates, this difference is likely a chance result. Mild hypercalcemia was common with calcitriol therapy, as was mild hypercalciuria (59% of patients vs. 10% controls), but there were no significant differences between groups in serum creatinine after 2 years. These data suggest calcitriol has a role in reducing proximal femur bone loss after cardiac or lung transplantation but treatment needs to be continued beyond 1 year.

Adrenal Cortex Hormones↗
PubMed2000

Postmenopausal osteoporosis treatment guidelines.

BACKGROUND: Several years ago, Osteoporosis Australia published Guidelines for the management of osteoporosis. Since then significant advances in our understanding of the treatment of osteoporosis have been published. The importance of this is heightened as early diagnosis is now possible with precise methods of bone density measurement. OBJECTIVE: This article presents updated guidelines developed on behalf of Osteoporosis Australia for the treatment of postmenopausal osteoporosis to help general practitioners identify those women at risk and to review current treatment strategies. DISCUSSION: Osteoporosis and its associated problems are major health concerns in Australia, especially with an ageing population. While important principles of management are still considered to be maximising peak bone mass and prevention of postmenopausal bone loss by oestrogen therapy, new clinical trial data about drugs such as raloxifene and the bisphosphonates have recently become available and the relative role of various agents is gradually becoming clearer.

Accidental Falls↗