Fracture prevention strategies in patients presenting to Australian hospitals with minimal-trauma fractures: a major treatment gap.

BACKGROUND: The aim of this study was to examine current fracture prevention strategies through the recognition, investigation and treatment of osteoporosis in patients presenting to acute hospitals with minimal-trauma fracture. METHODS: A retrospective audit using a standardized database was conducted in 16 Australian hospitals. This involved 1829 cases of minimal-trauma fracture initially presenting to hospital emergency departments during 2003-2005. Cases of minimal-trauma fracture were retrospectively identified using diagnosis-related group fracture codes and case record review at each site. Relevant data were entered into a standardized database and analysed centrally and independently. Risk factors for osteoporosis, investigations, interventions and discharge follow up were recorded. RESULTS: The percentage of minimal-trauma fracture patients who underwent investigation or initiated therapy designed to prevent subsequent minimal-trauma fracture was obtained. Less than 13% of patients presenting to hospital with minimal-trauma fractures had risk factors for fracture identified. Ten per cent were appropriately investigated, 12% were commenced on calcium and 12% on vitamin D. Eight per cent started bisphosphonates and 1% selective oestrogens receptor modulators in the acute setting. CONCLUSION: Most patients presenting to Australian hospitals with minimal-trauma fracture are neither investigated nor treated for osteoporosis. As this group is at high risk of subsequent fracture, this is a missed opportunity to reduce fracture burden.

A randomized, double-blind, placebo-controlled trial of intravenous zoledronic acid in the treatment of thalassemia-associated osteopenia.

Beta-thalassaemia major is associated with low bone mass and fractures. We conducted a 2 year randomized controlled trial of zoledronic acid 4 mg administered intravenously every 3 months or placebo in the treatment of beta-thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university hospitals with a T score of less than -1.0 at either the lumbar spine or hip, and 23 subjects completed the study (17 M, 6 F). Treatment groups did not differ significantly with respect to bone mineral density (BMD), age, height, weight and body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral reek, total hip and total body. After two years average lumbar spine BMD was 8.9% greater (95%CI 2.3-15.5%, P = 0.011), average femoral neck BMD was 9.1% greater (95%CI 5.5-12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5-12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7-6.8%, P < 0.0001) in the treated group compared to placebo. The absolute change in BMD from baseline to 2 years and the annualized rate of change of BMD was significantly greater in treated patients at all four sites. Age, gender, height, weight and BMI did not interact with the effect of treatment and so unadjusted data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and increases BMD in beta-thalassaemia-associated osteopenia.

The control of ovulation in mothers of dizygotic twins.

Dizygotic twinning is familial, suggesting that there may be an inherited abnormality of the control of ovulation that predisposes to double ovulation and, therefore, dizygotic twins. The present study examines 17 mothers of dizygotic twins (MODZT) and 8 control mothers of singletons by daily blood sampling throughout an entire menstrual cycle. Blood samples were assayed for LH, FSH, estradiol, progesterone, and inhibin. The process of follicular development was followed by transvaginal ultrasound. The pituitary LH response to iv GnRH was also assessed. Three of the 16 MODZT double ovulated during the study compared to none of the 8 control mothers (P < 0.05). The number of small follicles (<6 mm) declined significantly in control women at midcycle, but not in MODZT. There was no significant difference in serum FSH, LH, estradiol, or inhibin levels between the 2 groups at any stage of the menstrual cycle. During the follicular phase, serum progesterone levels were significantly higher in MODZT. The response to GnRH stimulation was not different between MODZT and controls. In conclusion, this study demonstrates an increased tendency to double ovulate in MODZT that may be due to a reduced rate of atresia in advanced follicles. Furthermore, the elevated progesterone levels in MODZT during the follicular phase suggest altered intrafollicular steroidogenesis that is independent of gonadotropins.

Determinants of forearm mineral density and its correlation with fracture history in women.

In order to evaluate the role of single photon absorptiometry (SPA) in the prediction of osteoporotic fracture risk, 1935 women, referred for measurement of forearm mineral density (FMD) at the distal radial site, were studied by questionnaire in a cross-sectional design. There was no significant decline in FMD until the age of 47, after which there was a linear decline with age of about 1.2% per year. There was no relationship between age and FMD, or forearm mineral content (FMC), in premenopausal women. There was a fall in FMD with the number of years since menopause, after correcting for the effects of age, of approximately 0.5% per year. Body weight was positively correlated with FMC in postmenopausal women. The duration of exposure to hormone replacement therapy (HRT) was positively correlated with FMD, and the magnitude of this effect was reduced the longer the delay between the onset of the menopause and the commencement of HRT. There was no significant association of FMD with calcium intake, weight-bearing exercise, tobacco or alcohol consumption, or family history of osteoporosis. FMD was significantly lower in postmenopausal women who reported fractures after the age of 25, after correcting for age and years postmenopause. In conclusion, a low FMD is predictive of a past history of fractures and may therefore be capable of predicting future fracture risk.

Development and validation of a radioimmunoassay for follistatin in human serum.

OBJECTIVE: Follistatin (FS/FSH-suppressing protein/activin-binding protein) is a single-chain glycoprotein, structurally distinct from inhibin, that has been shown to have inhibin-like activity in suppressing FSH secretion both in vivo and in vitro. The aim of these studies was to develop and validate a radioimmunoassay (RIA) for FS in human serum, and to describe the physiological variations of serum FS in humans. PATIENTS: Serum was collected from normal men, and normal women in the follicular and luteal phases of the menstrual cycle. Clinical samples were also collected from male patients with hypogonadism, post-menopausal women and pregnant women in the first, second and third trimesters. MEASUREMENTS: A RIA for FS in human serum was developed using antisera raised against purified bovine FS and using bovine FS as tracer and standard. Serial dilutions of serum were non-parallel to purified bovine FS standard in the RIA. The addition of sodium dodecyl sulphate (SDS 0.05%) to the assay buffer resolved the non-parallelism suggesting that the interference of serum in the RIA was an assay matrix effect. To characterize the serum FS immunoactivity further, serum was fractionated by gel filtration on Sephadex G-100. At neutral pH, FS immunoactivity eluted as a major peak in the molecular weight range > 200 kDa. In 0.1 M HCl, a second peak of FS immunoactivity eluted in the molecular weight range 30-60 kDa consistent with the known sizes of FS. This suggested that FS was dissociating from a larger complex. Fractions taken from the low molecular weight region diluted in parallel with bovine FS in contrast with fractions from the high molecular weight region which were non-parallel. It is concluded that the non-parallelism of human serum in the FS RIA is due to the binding of serum FS to an unknown high molecular weight factor. This interference is eliminated by the inclusion of 0.05% SDS in the assay buffer. The RIA in 0.05% SDS has been applied to the description of the normal and pathophysiological variations of FS in human serum. RESULTS: There were no significant differences between FS levels in serum from hypogonadal men, normal women in the follicular phase of the menstrual cycle, post-menopausal women and pregnant women from the first, second and third trimesters. FS levels in serum of women in the luteal phase of the menstrual cycle were significantly lower than all other groups. FS levels in normal men were significantly higher than those in both luteal phase women and women in the first trimester of pregnancy (P < 0.05). CONCLUSIONS: These findings argue against a role for circulating follistatin in the control of gonadotrophin secretion and suggest that the gonads and/or conceptus are not the primary source of follistatin immunoactivity in serum. The lower follistatin levels in the luteal phase of the menstrual cycle remain unexplained.