Estimation of lean body weight in older women with hip fracture.

OBJECTIVE: Lean body weight (LBW) decreases with age while total body fat increases, resulting in altered drug pharmacokinetics. A semi-mechanistic equation estimating LBW using height, weight and sex has been developed for potential use across a wide range of body compositions. The aim of this study was to determine the ability of the LBW equation to estimate dual energy x-ray absorptiometry-derived fat free mass (FFM(DXA)) in a population of older women with recent hip fracture. METHODS: Baseline, four and 12 month data obtained from 23 women enrolled in the Sarcopenia and Hip Fracture study were pooled to give 58 measurements. LBW was estimated using the equation: LBW (kg) = (9270 x Wt) / (8780 + (244 x BMI)). Body composition was classified as: 'normal' (BMI <25kg/m(2) and not sarcopenic), 'overweight-obese' (BMI >25kg/m(2) and not sarcopenic), 'sarcopenic' (sarcopenic and BMI <25kg/m(2)), or 'sarcopenic-obese' (sarcopenic and BMI >25kg/m(2)). The ability of the LBW equation to predict FFMDXA was determined graphically using Bland-Altman plots and quantitatively using the method of Sheiner and Beal. RESULTS: The mean ± SD age of female participants women was 83±7 years (n=23). Sarcopenia was frequently observed (65.2%). Bland-Altman plots demonstrated an underestimation by the LBW equation compared to FFMDXA. The bias (95% CI) and precision (95% CI) calculated using the method of Sheiner and Beal was 0.5kg (-0.7, 1.66kg) and 4.4kg (-3.7, 12.4kg) respectively for pooled data. CONCLUSION: This equation can be used to easily calculate LBW. When compared to FFMDXA, the LBW equation resulted in a small underestimation on average in this population of women with recent hip fracture. The degree of bias may not be clinically important although further studies of larger heterogeneous cohorts are needed to investigate and potentially improve the accuracy of this predictive equation in larger clinical cohorts.

A sensitive stain for aluminum in undecalcified cancellous bone.

Aluminum is known to accumulate with age in bone and other tissues of humans, even in the absence of renal disease. Our study aimed to develop a histological staining method sufficiently sensitive to detect aluminum in plastic sections of undecalcified bone biopsies from healthy volunteers as well as from patients with renal and non-renal bone diseases. We used quantitative histomorphometry to measure the percentage of trabecular surface stained by aluminum and found that our new method was approximately 50% more sensitive for detecting aluminum than the Acid Solochrome Azurine (ASA) method which in turn was significantly more sensitive than the Aluminon method. Aluminon is widely used in pathology laboratories for diagnostic purposes despite concerns in the literature about Aluminon's limited sensitivity for aluminum. Our histomorphometric results showed that the newly developed method stained approximately 10% of the trabecular surface in bone sections from healthy controls, 38% from renal patients, 26% from patients with vitamin D deficiency, and 29% from patients with osteoporosis. Histomorphometric measurements of aluminum-stained trabecular surfaces in sections stained with ASA were consistent with those obtained in Walton-stained sections but proportionately lower. Moreover, the Walton and ASA methods stained aluminum at similar locations in adjacent bone sections. As the ASA and Walton methods are considerably more sensitive for bone aluminum than the Aluminon method, we recommend that either of them should be used in place of the Aluminon method for routine diagnostic purposes.

The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study.

BACKGROUND: Prostate carcinoma therapy with combined androgen blockade may result in high bone-turnover with significant bone loss. This study was undertaken to evaluate the antiosteoporotic efficacy of intravenous pamidronate in a double blind, randomized, placebo-controlled, crossover study. METHODS: Twenty-one consecutive men with metastatic prostate carcinoma who were receiving combined androgen blockade with a long-acting gonadotropin-releasing hormone agonist (gosarelin acetate) and an androgen antagonist (flutamide or bicalutamide) were evaluated at baseline and at 6 and 12 months after therapy. They were randomly assigned to receive a single intravenous infusion of 500 mL of normal saline solution diluted with either pamidronate (90 mg) or placebo at baseline and with a crossover at 6 months. Lumbar-spine bone-mineral densities (BMDs) were measured by spinal quantitative computed tomography (QCT), femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover were measured by noninvasive methods. Data on 10 men with localized prostate carcinoma who were treated with radiotherapy alone, over the same period, was collected for comparison studies. RESULTS: The mean age of the men was 75.1 years +/- 1.6 years. One man withdrew from the study because of deteriorating health, and two died from metastatic disease within the first 6 months. Combined androgen blockade normalized serum prostate-specific antigen activities (from an initial mean value of 86.2 ng/mL +/- 10.1 ng/mL) and maintained serum free testosterone concentrations in the hypogonadal range (< 2.2 pmol/L) in all men throughout the study. Treatment with pamidronate resulted in a 7.8% +/- 1.5% increase in mean lumbar spine QCT from 79.4 mg/cm(3) (95% confidence interval [CI], 64-94 mg/cm(3)) to 85.6 mg/cm(3) (95% CI, 70-101 mg/cm(3)) (P = 0.0005) and a 2% +/- 0.9% increase in mean total femoral neck DXA from 0.98 g/cm(2) (95% CI, 0.90 -1.05 g/cm(2)) to 1.0 mg/cm(2) (95% CI, 0.91-1.08 g/cm(2)) (P = 0.02). Conversely, treatment with placebo, resulted in a 5.7% +/- 1.6% decrease in mean lumbar spine QCT and a 2.3% +/- 0.7% decrease in mean total femoral neck DXA (P = 0.0001 and P = 0.0007 for the comparison of percentage change between the pamidronate and placebo treatments). After pamidronate therapy, serum bone Gla-protein concentrations decreased by 16.8% +/- 5.9%, and urinary deoxypyridinoline excretion rates decreased by 18.5% +/- 12.8% (P < 0.01 respectively for the comparison between pamidronate and placebo treatment). CONCLUSIONS: This study demonstrated that a single intravenous infusion of pamidronate (90 mg) significantly reduced the high bone turnover and bone loss (for at least 6 mos) in men with prostate carcinoma who had been rendered hypogonadal with combined androgen blockade therapy.

Percutaneous vertebroplasty: a novel treatment for acute vertebral fractures.

Acute vertebral fracture is a painful and debilitating complication of osteoporosis which has been extremely difficult to manage. Percutaneous vertebroplasty--injecting cement to stabilise the fractured end plate--represents a major management breakthrough. We report the first four patients with osteoporotic vertebral fractures treated by this technique at our hospital. They are, to our knowledge, among the first to be successfully treated in this way in Australia.

Hip fracture in elderly men: prognostic factors and outcomes.

OBJECTIVE: To examine prognostic factors and outcomes after hip fracture in men aged 60 years and older. DESIGN AND SETTING: Cohort study of all men presenting to St George Hospital (a 650-bed tertiary care centre) with hip fractures in 1995, recruited retrospectively from medical records and evaluated prospectively at six and 12 months after fracture. PATIENTS: 51 men aged 60 years or more (and, for comparison, 51 age-matched women) who presented with hip fracture not caused by high impact injuries or local bone disease. MAIN OUTCOME MEASURES: Prognostic factors (such as pre-existing illness and osteoporotic risk factors) and outcome data (such as fracture-related complications, mortality, and level of function as measured by the Barthel index of activities of daily living at six and 12 months postfracture). RESULTS: Median age of the 51 men was 80 years (interquartile range, 74-86 years); four were aged under 70 years. Outcome assessment was possible for 41 men (80%). Similar proportions of men and women came from institutions (32% v. 28%), and similar additional proportions required institutionalisation after discharge (18% v. 14%). Fracture-related complications affected similar proportions of men and women (30% v. 32%), and mean length of hospital stay was similar. Fourteen per cent of men died in hospital compared with only 6% of women (P = 0.06). Men had more risk factors for osteoporosis (P < 0.01). Physical functioning (measured by the Barthel index) deteriorated significantly in men from 14.9 at baseline to 13.4 at six months (P < 0.05) and 12.4 at 12 months (P < 0.05) after fracture. CONCLUSION: Compared with women, elderly men presenting with hip fracture have higher mortality and have more risk factors for osteoporosis. Like women with hip fracture, men are usually fragile, with pre-existing medical illness and fracture-related complications contributing to their overall poor outcomes.

Reproducibility of lateral spine scans using dual energy X-ray absorptiometry.

Reproducibility of lateral spine dual energy X-ray absorptiometry (LAT DEXA) scans using a Lunar DPX-L scanner was assessed in a cadaveric phantom and in patients. One hundred phantom measurements over 7 months demonstrated a longitudinal stability of 1.7% (coefficient of variation, CV). Additional scans were performed with the phantom rotated by up to 20 degrees in each of the three orthogonal planes to assess the effects of variable patient positioning. Horizontal and vertical rotation of the spine had little effect on the estimated bone mineral density (BMD), however, axial rotation of greater than 8 degrees led to errors in the BMD measurement. One hundred consecutive patients had two lateral scans performed within 1 month. BMD (range 0.10-1.6 g/cm2) was determined for each scan by one operator. Significant overlap from ribs and pelvis was often seen with L2 and L4 vertebrae but one vertebra (L3) could be measured in every case. Intraoperator and interoperator variability was assessed by three experienced operators, each analyzing 10 patients' scans on five separate occasions, and was found to be less than 1.1% for a single vertebra. BMD estimation of vertebral bodies and midslices by lateral DEXA scans (CV% of 3.8% and 4.6%) have a 95% confidence interval of 0.074 g/cm2 and 0.096 g/cm2, respectively for two vertebrae. This variability is due mainly to axial rotation, with operator variability, horizontal rotation, and vertical rotation having little effect on BMD estimation.

The acute effects of glucosidase inhibition on post-meal glucose increments in insulin-dependent diabetics.

The effects of glucosidase inhibition on postprandial glucose tolerance was studied in 11 insulin-dependent diabetics. In comparison with placebo, 50 mg miglitol was able to lower the incremental glucose response significantly at 30 minutes and 60 minutes when insulin was injected: (i) 30 minutes before the meal (2,3 +/- 0,5 mmol/l v. 0,37 +/- 0,2 mmol/l; P less than 0,001; and 5,0 +/- 0,7 mmol/l v. 1,1 +/- 0,8 mmol/l; P less than 0,001); and (ii) immediately before the meal (2,3 +/- 0,5 mmol/l v. 2,2 +/- 0,9 mmol/l; P less than 0,001) respectively. The incremental glucose area under the curve when insulin was injected 30 minutes before breakfast was also significantly reduced on miglitol in comparison with placebo (0,67 +/- 0,15 mmol/l v. 0,16 +/- 0,14 mmol/l; P less than 0,01). The effect of miglitol was more evident when insulin was injected 30 minutes before rather than immediately before the meal. No significant adverse effects were encountered. It is concluded that: (i) miglitol safely reduces the early post-meal glucose increments in insulin-dependent diabetics; and (ii) its effect enhances the hypoglycaemic response of an appropriately timed injection of insulin.

Hypercalcaemia in sarcoidosis co-existing with primary hyperparathyroidism. A case report.

Patients presenting with hypercalcaemia caused by the co-existence of sarcoidosis and primary hyperparathyroidism may present a diagnostic problem. Tests for sarcoid activity, together with the cortisone suppression test and an estimation of the immunoreactive parathyroid hormone level are all necessary to differentiate between those conditions.

Time-dependent changes in serum gastrin measurements after parathyroidectomy.

A prospective study involving 7 patients with primary hyperparathyroidism and hypergastrinaemia was conducted to assess the time-dependent change in serum gastrin value before and after parathyroidectomy and to determine at which postoperative stage persistent hypergastrinaemia may be indicative of an associated gastrinoma (Zollinger-Ellison syndrome). Five of the 7 patients had hypergastrinaemia in the early postoperative period. One patient had a strikingly high serum gastrin level pre-operatively (1,500 pg/ml). The mean serum gastrin value declined to within the normal range 6 weeks after parathyroidectomy, except in 1 patient who had a gastrinoma. It is concluded that hypergastrinaemia in patients with primary hyperparathyroidism should only be considered significant if pre-operative gastrin levels are strikingly supranormal and/or levels fail to normalise by the 6th postoperative week.

Hepatic osteodystrophy. Static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver disease.

To study the pathogenesis of osteoporosis in patients with chronic liver disease, we performed dynamic bone histomorphometry and measured serum bone Gla-protein in 80 patients with various types of chronic liver disease. These results were compared with results obtained in 40 healthy controls. Mean trabecular bone volume and mean trabecular thickness were significantly reduced in both men and women with chronic liver disease (p less than 0.001 for both measurements in men and p less than 0.01 for both measurements in women). Osteoporosis as defined by histologic parameters was present in 17 (21%) patients with no significant differences in prevalence rates among the various hepatic disorders. No patient had histologic evidence of osteomalacia, although mineralization lag times were prolonged (p less than 0.01 for men and women). Bone formation rates were significantly reduced in 46 (57%) patients, and unlike the static measurements, were related to the type and severity of the underlying liver disease. Patients with alcoholic liver disease, hemochromatosis, and cholestatic liver disease had lower bone turnover rates and osteoblastic surfaces (p less than 0.001 and p less than 0.05, respectively) than patients with chronic active hepatitis. Furthermore, the presence of hepatic cirrhosis was associated with diminished bone formation and lower osteoblast surfaces. Serum bone Gla-protein levels were significantly correlated with bone formation rates and osteoblast surfaces (r = 0.585 and r = 0.434, respectively). A reduction in osteoblast surfaces has not previously been demonstrated in liver disease. This reduction and the associated impairment of osteoblastic activity may contribute to the pathogenesis of osteoporosis and can be assessed by the measurement of serum bone Gla-protein.

Hypercalcaemia in the Johannesburg Hospital. Differential diagnosis and physician awareness of primary hyperparathyroidism.

A 1-year retrospective study of all serum profiles of patients with hypercalcaemia analysed at the Johannesburg Hospital was carried out to ascertain the causes of hypercalcaemia and physician awareness of primary hyperparathyroidism. Hypercalcaemia was found in 560 subjects (2.9% of 19,200), but in 147 of these (26%) this was not confirmed by repeat estimations. Malignant tumours were the commonest cause (38.4%) and accounted for the most severe hypercalcaemia (mean serum calcium 2.93 mmol/l). Renal disease resulted in significant hypercalcaemia, at times requiring parathyroidectomy. Drug-associated hypercalcaemia was usually mild and reversible on drug withdrawal. Although primary hyperparathyroidism occurred in 21.3% of cases, overall physician awareness of the disease was poor (39%). 'Incidental' profile hypercalcaemia (P less than 0.005) and hypertension (P less than 0.005) were frequent presenting features in this study. Renal disease (P less than 0.001) occurred infrequently.

Disseminated Blastomyces dermatitidis infection in a non-endemic area. A case report.

In areas where tuberculosis is endemic other causes of respiratory infection are often overlooked. A pulmonary infiltrate associated with skin lesions without a microbiological diagnosis of tuberculosis should arouse suspicion of a fungal infection. This was demonstrated in a patient in whom Blastomyces dermatitidis, a rare pathogen in southern Africa, was isolated.