Search PubMed⌕ Search

Biomedical subjects

P N Sambrook

Publications and source records attributed to P N Sambrook.

At least 19 recordsLinked to original sources
PubMed2007

Influence of fall related factors and bone strength on fracture risk in the frail elderly.

INTRODUCTION: When subjects are selected on the basis of fall risk alone, therapies for osteoporosis have not been effective. In a prospective study of elderly subjects at high risk of falls, we investigated the influence of bone strength and fall risk on fracture. METHODS: At baseline we assessed calcaneal bone ultrasound attenuation (BUA) as well as quantitative measures of fall risk in 2005 subjects in residential care. Incident falls and fractures were recorded (median follow-up 705 days). RESULTS: A total of 6646 fall events and 375 low trauma fracture events occurred. The fall rate was 214 per 100 person years and the fracture rate 12.1 per 100 person years. 82% of the fractures could be attributed to falls. Although fracture rates increased with decreasing BUA (incidence rate ratio 1.94 for lowest vs. highest BUA tertile, p<0.002), incident falls also affected fracture incidence. Subjects who fell frequently (>3.15 falls/per person year) were 3.35 times more likely to suffer a fracture than those who did not fall. Some fall risk factors such as balance were associated with the lowest fracture risk lowest in the worst performing group. Multivariate analysis revealed higher fall rate, history of previous fracture, lower BUA, lower body weight, cognitive impairment and better balance as significant independent risk factors for fracture. CONCLUSIONS: In the frail elderly, both skeletal fragility and fall risk including the frequency of exposure to falls are important determinants of fracture risk.

Accidental Falls↗
PubMed2006

Calcaneal ultrasound but not bone turnover predicts fractures in vitamin D deficient frail elderly at high risk of falls.

BACKGROUND: Biochemical markers of bone turnover have been reported to predict fracture risk independent of bone mass in postmenopausal women. We investigated their use in predicting fractures in the frail elderly. METHODS: Cases were 151 low trauma fractures. For each case, a control was selected marched for sex, age, institution type and follow-up period. We measured two bone resorption markers (serum ICTP and serum CTX-I) and two bone formation markers (serum PINP and serum BAP). Quantitative Ultrasound (QUS) was measured in the calcaneus. Fractures were ascertained by x-ray reports. RESULTS: The mean age of subjects was 86.8 years (+/- 5.8 SD) and 86% were female. 76% had hypovitaminosis D (a serum 25 hydroxy vitamin D (25OHD) level < 39 nmol/L) and 81% had BUA < 67.4 dB/MHz (corresponding to a BMD T-score < -2.5). No significant differences in bone turnover markers were detected between fracture cases and their matched controls. In contrast, there was a significant difference between cases and controls for both broadband ultrasound attenuation (BUA) and velocity of sound (VOS) (both P < 0.05). These results remained the same after adjusting for weight, lower leg length and walking aids as well as the higher falls incidence in cases than controls (average 2.7 vs 0.9 falls respectively; P < 0.001) during the follow-up period. CONCLUSION: In the frail elderly with vitamin D deficiency and high falls risk, calcaneal ultrasound but not markers of bone turnover were associated with fractures.

Accidental Falls↗
PubMed2006

Etanercept and sulfasalazine, alone and combined, in patients with active rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison.

OBJECTIVE: To compare the efficacy and safety of etanercept and sulfasalazine, alone and in combination, in patients with active rheumatoid arthritis despite sulfasalazine treatment. METHODS: A double-blind, randomised study in adult patients with active rheumatoid arthritis despite stable sulfasalazine (2-3 g/day) treatment. The primary end point was a 20% response by the American College of Rheumatology (ACR) criteria at 24 weeks. RESULTS: At baseline, the three treatment groups (sulfasalazine, n = 50; etanercept, n = 103; etanercept and sulfasalazine, n = 101) were comparable for demographic variables and disease activity. Lack of efficacy was the primary reason for discontinuation (sulfasalazine, n = 12; etanercept, n = 1; etanercept and sulfasalazine, n = 4; p<0.001). Significantly more patients receiving etanercept, alone or in combination (74% for each), achieved ACR 20 responses at 24 weeks than those receiving sulfasalazine (28%; p<0.01). Similarly, more patients in the etanercept groups achieved ACR 50 and ACR 70 responses than those in the sulfasalazine group (p<0.01). In the groups receiving etanercept, significant differences in the ACR core components were observed by week 2 compared with those receiving sulfasalazine alone (p<0.01). The incidences of several common adverse events (headache, nausea, asthenia) were lower with etanercept alone than with the combination (p<0.05), but infections and injection site reactions were higher with etanercept alone (p<0.05). The safety profiles of both etanercept treatment groups were comparable with previous experience of etanercept. CONCLUSIONS: For all efficacy variables assessed, etanercept alone or in combination with sulfasalazine resulted in substantial and similar improvement in disease activity from baseline to week 24 compared with sulfasalazine alone in patients with active rheumatoid arthritis despite their sulfasalazine treatment. All three treatments were generally well tolerated.

Adult↗
PubMed2005

A multivariate regression model predicted falls in residents living in intermediate hostel care.

BACKGROUND AND OBJECTIVE: To evaluate whether individual falls risk could be predicted in a frail elderly population. STUDY DESIGN AND SETTING: We developed and tested an assessment tool and falls risk score for predicting falls based on a multivariate regression model in a prospective cohort study of intermediate care residents. RESULTS: During the follow-up period, 1,736 falls by 1,107 subjects were recorded with an average of 170 falls per 100 person-years. Fifty percent of the study population had at least one fall within a year. Significant independent risk factors were poor balance, cognitive impairment, incontinence, higher illness severity rating, and older age. Twenty-two percent of participants with a falls risk score > or =7 accounted for 42% of the total falls, with a falls rate of 317 per 100 person-years. This rate was a sixfold increase from the falls rate of 52 per 100 person-years observed in participants with a score < 3. A high score (> or =7) indicated almost a 2 in 3 chance of falling, while a low score (<3) indicated approximately a 1 in 7 chance of falling within 6 months. CONCLUSION: The assessment tool and falls risk score could identify individuals in this frail elderly population at high risk of falls.

Accidental Falls↗
PubMed2005

Determinants of health-related quality of life in institutionalised older persons in northern Sydney.

It is recognised that the focus of health-care interventions for frail older persons should not be restricted to increasing longevity, but should encompass measures aimed at improving or maintaining the health-related quality of life (HRQoL) of these individuals. We studied the HRQoL profile of 612 frail older persons residing in nursing homes and hostels in northern Sydney, Australia, and sought to ascertain some of the factors that affect their perceived quality of life. Our findings suggest that common health states that may cause loss of independence and dignity (e.g. presence of osteoarthritis, presence of urinary incontinence, previous fracture, Parkinson's Disease and increasing frailty as reflected by residence in nursing homes) are strongly, and independently, associated with the HRQoL of institutionalised older persons. Some of these conditions may be amenable to intervention.

Aged↗
PubMed2005

How to prevent steroid induced osteoporosis.

The first choice for prevention of corticosteroid osteoporosis is a potent oral bisphosphonate-for example, alendronate or risedronate. Intravenous bisphosphonates should be considered for patients intolerant of the oral route. For patients receiving chronic low dose corticosteroids treatment with calcium and vitamin D may prevent further bone loss. Use of parathyroid hormone is promising.

Calcium↗
PubMed2004

Alendronate in the prevention of osteoporosis: 7-year follow-up.

In a 3-year study followed by a 2-year open-label extension, alendronate sodium (ALN) maintained or increased bone mineral density (BMD) in 445 recently postmenopausal women with a spine BMD T-score >-2. In a second 2-year extension, 84 women previously treated with either 5 or 10 mg ALN daily during the first 3 years and 5 mg ALN during the first extension (group A) were randomized to either 5 mg ALN or placebo (PBO). Another group of 59 women (group B) received 20 mg ALN during the first 2 years, PBO during year 3, and were then followed up without treatment during years 4-7. In group A, continuous ALN treatment for 7 years increased spine and trochanter BMD by 2.7-4.1 and 3.3-4.2%, respectively, while femoral neck BMD was maintained. Patients initially receiving 10 mg ALN maintained total body BMD, whereas those treated with 5 mg ALN experienced a small but significant loss after 7 years. Among women who received ALN 5 mg during years 4-7, those who had been treated with ALN 10 mg in the first 3 years had slightly greater increases in BMD at most sites at the end of the study, compared with women who received ALN 5 mg during the first 3 years. During years 6-7, patients who switched to PBO during the previous 2 years showed a significant loss in femoral neck BMD, whereas changes at the other sites were not significant. Women in group B showed significant loss in BMD at all skeletal sites during years 4-7, when they received no treatment. In conclusion, ALN 5 or 10 mg daily for up to 7 years prevents bone loss in recently postmenopausal women. Patients started on ALN 10 mg appear to gain more BMD than those initially treated with 5 mg ALN. Early postmenopausal women who discontinue ALN after 2 years of treatment experience significant bone loss at all skeletal sites despite the higher (20 mg) initial dosing. The ALN was generally well tolerated during 7 years of treatment.

Adult↗
PubMed2004

Quantitative ultrasound measurements of bone: measurement error, discordance, and their effects on longitudinal studies.

The performance of quantitative ultrasound (QUS) for the assessment of osteoporotic fracture must be fully defined if it is to be used in the clinical setting. We have examined the precision and reproducibility of two ultrasound instruments in 1,267 institutionalized elderly men and women (mean age 82.1 and 85.9 years, respectively). Measurement of BUA and VOS was reliable, least significant change for BUA being 2.4% and for VOS 0.3% using the CUBA McCue instrument and 2.7% for BUA using the Metra QUS-2. Importantly, age was not found to influence the precision of either parameter. Comparison of the instruments showed the QUS-2 measures BUA higher than the CUBA by 1.9 dB/MHz (+/-9.55 dB/MHz). Moreover classification of individuals as osteoporotic by machine-derived T-score was different between instruments (kappa = 0.44 in men and kappa = 0.62 in women). Fifty-six residents were remeasured by CUBA after 2.2 years; BUA was observed to decrease by 5.2% (+/-16.5%, p = 0.02) without significant change in VOS, suggesting BUA is more useful in longitudinal studies. In conclusion, ultrasound measurements were highly reliable and sensitive to longitudinal change even in the very elderly. However, diagnosis by T-score criteria was instrument specific, and such criteria should be interpreted with caution in the assessment of fracture risk.

Aged↗
PubMed2004

Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International.

OBJECTIVES: Alendronate and raloxifene are antiresorptive agents with different mechanisms of action, each used to treat osteoporosis in postmenopausal women. This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density. DESIGN: Randomized, double-masked, double-dummy multicentre international study. SETTING: Clinical trial centres in Europe, South America and Asia-Pacific. SUBJECTS: A total of 487 postmenopausal women with low bone density, based on bone mineral density (BMD) of the lumbar spine or hip (T-score < or =-2.0). Interventions. Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months. MAIN OUTCOME MEASURES: Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting. RESULTS: Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months. Lumbar spine BMD increased 4.8% with alendronate vs. 2.2% with raloxifene (P < 0.001). The increase in total hip BMD was 2.3% with alendronate vs. 0.8% with raloxifene (P < 0.001). Reductions in bone turnover were significantly larger with alendronate than raloxifene. Overall tolerability was similar, however, the proportion of patients reporting vasomotor events was significantly higher with raloxifene (9.5%) than with alendronate (3.7%, P = 0.010). The proportion of patients reporting gastrointestinal events was similar between groups. CONCLUSION: In postmenopausal women with low bone density, improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene.

Alendronate↗
PubMed2004

Serum parathyroid hormone predicts time to fall independent of vitamin D status in a frail elderly population.

Very frail older people constitute an increasing proportion of ageing populations and often have vitamin D deficiency. Falls are frequent in this population and have usually been associated with vitamin D deficiency. In this prospective study we measured serum 25-hydroxyvitamin D (25OHD), serum PTH, and falls in 637 ambulatory subjects living in institutional aged care facilities (intermediate-care hostels or nursing homes). The study sample comprised 121 men (mean age, 82.1 yr) and 516 women (mean age, 86.7 yr). Two hundred and seventy-four subjects fell one or more times over a mean duration of follow-up of 10.2 months. Vitamin D deficiency, defined as a serum 25OHD level below 39 nmol/liter was present in 73.6%. Baseline serum 25OHD and PTH were significantly associated with falls in univariate analyses. In multivariate analyses that also corrected for balance and health status, PTH remained a significant predictor of falls independent of 25OHD. Serum PTH is a predictor of time to first fall in the frail elderly independent of vitamin D status and measures of general health.

Accidental Falls↗
PubMed2004

Serum parathyroid hormone is associated with increased mortality independent of 25-hydroxy vitamin d status, bone mass, and renal function in the frail and very old: a cohort study.

Very frail older people constitute an increasing proportion of the aging population and often have vitamin D deficiency and impaired renal function. Primary hyperparathyroidism has been associated with increased mortality, but it is unclear whether secondary hyperparathyroidism is associated with increased mortality independent of renal function and vitamin D status. This study aimed to examine the effect of vitamin D deficiency and secondary hyperparathyroidism on mortality in frail older people after accounting for renal function and general measures of health. We evaluated 842 subjects (182 men with a mean age of 81.9 yr and 660 women with a mean age of 86.2 yr) living in residential aged care facilities in Sydney, Australia in a prospective, cohort study. Over a mean duration of follow-up of 31 months, 345 subjects died. Baseline serum 25-hydroxy vitamin D, serum PTH, and bone ultrasound attenuation were significantly associated with mortality in univariate and multivariate analyses (for PTH, a hazard ratio of 1.39 for time to death) after correcting for age and gender. In multivariate analyses that corrected for health status, nutritional status, and renal function, PTH remained a significant predictor of mortality but not 25-hydroxy vitamin D or bone ultrasound attenuation. Serum PTH appears to be associated with increased mortality in the frail elderly independent of vitamin D status, renal function, bone mass, and measures of general health. The mechanism of this effect requires further investigation.

Aged↗
PubMed2003

The association of cartilage volume with knee pain.

OBJECTIVE: Whilst the characteristic pathologic feature of OA is the loss of hyaline cartilage, prior studies have demonstrated a poor relationship between severity of reported knee pain and degree of radiographic change. The aim of this study was to examine the association between knee symptoms and MRI cartilage volume. DESIGN: A cross-sectional study was performed to assess the association between knee symptoms and MRI cartilage volume in an unselected, community based population. The subjects were 133 postmenopausal females. The subjects had a T2-weighted fat saturated sagittal gradient-echo MRI performed of their right knee. Femoral, tibial and patella cartilage volumes were measured using three-dimensional (3D) Slicer, a software that facilitates semi-automatic segmentation, generation of 3D surface models and quantitative analysis. Qualitative data relating to symptoms, stiffness, pain, physical dysfunction and the quality of life using the WOMAC were recorded. The statistical analyses conducted to determine measures of association between knee pain/symptoms and cartilage volume were correlation, multiple regression and inter-quartile regression. RESULTS: Assessment of the association between patella cartilage volume and the WOMAC domains showed an inverse relationship between patella cartilage volume and pain, function and global score in a model including body mass index, physical activity and leg extensor power (all P=0.01). Inter-quartile regression comparing the lowest 25% with highest 25% patella cartilage volume demonstrated a stronger inverse relationship (P=0.005). CONCLUSION: This study suggests that alterations in patella volume are associated with pain, function and global scores of the WOMAC. In participants with more knee pain, there was an association with severity of patella cartilage reduction. Other MRI cartilage volume features were not strongly associated with WOMAC sub-scores.

Aged↗
PubMed2003

Osteocyte viability with glucocorticoid treatment: relation to histomorphometry.

BACKGROUND: Glucocorticoid induced osteoporosis is a common clinical problem. OBJECTIVE: To determine the pathophysiology of glucocorticoid induced osteoarthritis at the organ level. METHODS: Iliac crest biopsy specimens were obtained from nine patients receiving prednisone treatment for rheumatoid arthritis. Osteocyte viability and histomorphometric indices were assessed. RESULTS: Compared with controls, glucocorticoid treated subjects had reduced trabecular thickness and increased erosion. The number of viable osteocytes was significantly decreased in glucocorticoid treated patients compared with controls. CONCLUSION: The impaired bone formation, increased erosion and, importantly, loss of viable osteocytes are all likely to contribute to the increased risk of fracture in these patients.

Aged↗
PubMed2002

Quantitative ultrasound of the calcaneus and falls risk in the institutionalized elderly: sex differences and relationship to vitamin D status.

Very frail older people constitute an increasing proportion of aging populations and are likely to contribute substantially to costs due to osteoporosis. Quantitative ultrasound (QUS) of the calcaneus is potentially a simple method for assessing fracture risk in frail elderly, but there have been few studies of male/female differences in QUS or its relationship to falls risk or vitamin D status, which is often subnormal in this population. We studied QUS, falls risk and serum 25(OH)-vitamin D in subjects living in institutional aged care facilities (hostels or nursing homes). The study sample comprised 294 men (mean age 81.2 years, range 65-102 years) and 899 women (mean age 86.7 years, range 65-104 years). Broadband ultrasound attenuation (BUA) and velocity of sound (VOS) were higher in men than women by approximately 30% and 2% respectively ( p<0.0001) and this difference was maintained at all ages. Serum 25(OH)D levels were higher in men than women ( p<0.001) but vitamin D deficiency was very common in both sexes and serum 25(OH)D was not associated with QUS in either sex. There was no significant decline in BUA or VOS with age in men; however, for women BUA declined by 2.8-4.7% per decade and VOS by 1% per decade (both p<0.001). Mean BUA T-scores were -1.55 and -2.48 at age 90 years in men and women. Quadriceps strength and weight but not serum 25(OH)D were significantly associated with BUA. These data suggest only minor loss occurs at the calcaneal site in BUA and VOS with very old age in either sex.

Accidental Falls↗
PubMed2002

Peak bone mass is increased in the hip in daughters of women with osteoarthritis.

The mechanism behind the inverse association between osteoporosis and osteoarthritis shown in large epidemiological studies remains unclear. Because both diseases often demonstrate a family history, the objective of the present study was to compare peak bone density in daughters categorized according to the presence or absence of hand osteoarthritis in their mothers. Radiographs of the hands were obtained in women aged 50-75 years from a well-defined community population group. X-rays were graded for hand osteoarthritis (OA) using the Kellgren and Lawrence criteria. In 60 daughters (mean age 33.6 years) of these women, bone mineral density (BMD) was measured at five regions of the hip and lumbar spine and quantitative ultrasound (QUS) at the calcaneus. Daughters whose mothers had hand OA (i.e., OA at either the carpometacarpal [CMC] or distal interphalageal [DIP] joints) had significantly higher mean BMD, when adjusted for body mass index (BMI) (5.1%-8.1%, p < 0.05), at all hip regions except the trochanter. However, differences in lumbar BMD and calcaneal QUS were not statistically significant. In multiple regression analysis, maternal hand OA status was found to be a significant predictor of daughters' hip BMD when daughters' BMI and mothers' BMD were included in the model. These findings suggest that the observation of higher BMD in older patients with OA may be due in part to achievement of a higher peak bone mass at some sites.

Adult↗
PubMed2002

Steroid-induced osteoporosis.

INTRODUCTION: Corticosteroids have major effects on calcium metabolism, leading to accelerated osteoporosis and fracture. METHODS: This review will attempt to summarise current knowledge about their effects in light of new information and important remaining questions, especially with respect to management of this common condition. RESULTS: Corticosteroids affect bone through multiple pathways, influencing both bone formation and bone resorption. Evidence from randomised trials suggests that postmenopausal women receiving corticosteroids are at greatest risk of rapid bone loss and consequent fracture and should be actively considered for prophylaxis. Based upon available evidence, the rank order of choice for prophylaxis would be a bisphosphonate followed by a vitamin D metabolite or hormone replacement. CONCLUSIONS: With early therapy, corticosteroid bone loss can be effectively prevented or reversed.

Adrenal Cortex Hormones↗