Parathyroid hormone(1-84) treatment of postmenopausal women with low bone mass receiving hormone replacement therapy.

Treatment of postmenopausal osteoporosis (PMO) is based primarily on antiresorptive agents, including hormone replacement therapy (HT). To evaluate whether anabolic therapy together with HT provides additional benefits in the treatment of PMO, we evaluated the effects of parathyroid hormone (PTH) 1-84 in postmenopausal women with low bone mineral density (BMD) who were receiving chronic (> or =6 months) HT. Subjects were randomized to receive 100 microg PTH(1-84) or placebo injections daily for 24 months (n = 90/group). The primary efficacy outcome was change from baseline in lumbar spine BMD. Secondary end points included changes in hip and distal radius BMD, bone turnover markers, and fracture incidence. The study was terminated early following recommendations regarding HT for PMO. At 18 months, the mean increase in lumbar spine BMD was 7.9% for PTH(1-84) subjects vs. 1.5% for those receiving HT alone; between-group differences were significant at 6 months and persisted throughout the study. Lumbar spine BMD increased in 94% of women receiving PTH(1-84) compared to 59% for HT alone. Femoral neck BMD and bone turnover markers were significantly higher in PTH(1-84)-treated subjects, but the changes in total hip and distal radius BMD were not significant. PTH(1-84) treatment was generally well-tolerated, with hypercalciuria, hypercalcemia, nausea, vomiting, and dizziness reported more frequently in the HT + PTH(1-84) group. In conclusion, addition of PTH(1-84) to stable HT produced marked increases in lumbar spine BMD and may represent an additional approach to the treatment of PMO women receiving HT.

A list of device-specific thresholds for the clinical interpretation of peripheral x-ray absorptiometry examinations.

The UK National Osteoporosis Society (NOS) has recently issued new guidelines on the use of peripheral x-ray absorptiometry (pDXA) devices in managing osteoporosis. The NOS guidelines recommend a triage approach in which patients' bone mineral density (BMD) measurements are interpreted using upper and lower thresholds specific to each type of pDXA device. The thresholds are defined so that patients with osteoporosis at the hip or spine are identified with 90% sensitivity and 90% specificity. Patients with a pDXA result below the lower threshold are likely to have osteoporosis at the hip or spine, patients with a result above the upper threshold are unlikely to have osteoporosis, while those between the two thresholds require a hip and spine BMD examination for a definitive diagnosis. This report presents data from a multicenter study to establish the triage thresholds for a range of pDXA devices in use in the UK. The subjects were white female patients aged 55-70 years who met the normal referral criteria for a BMD examination. For each device, at least 70 women with osteoporosis at the hip or spine and 70 women without osteoporosis were enrolled. All women had hip and spine BMD measurements using axial DXA systems that were interpreted using the National Health and Nutrition Examination Survey (NHANES) reference range for the hip and the manufacturers' reference ranges for the spine. Data are presented for five different devices: the Osteometer DTX-200 (forearm BMD), the Schick AccuDEXA (hand BMD), the GE Lunar PIXI (heel BMD), the Alara MetriScan (hand BMD), and the Demetech Calscan (heel BMD). The clinical measurements were supplemented by theoretical modeling to estimate the age dependence of the triage thresholds and the effect of the correlation coefficient between pDXA and axial BMD on the percentage of women referred for an axial BMD examination. In summary, this study provides thresholds for implementing the new NOS guidelines for managing osteoporosis using pDXA devices. The figures reported apply to postmenopausal white women aged 55-70 years who meet the conventional criteria for a BMD examination. The results confirm that the thresholds are specific to each type of pDXA device and that the NOS triage algorithm requires 40% of women to have an axial DXA examination.

Bone density at the os calcis: reference values, reproducibility, and effects of fracture history and physical activity.

AIMS: To establish reference values for bone mineral density (BMD) measured at the os calcis (OC) in healthy UK Caucasian children. Secondary objectives were to assess the reproducibility of the measurement and the effects of fracture history and habitual physical activity. METHODS: A total of 403 children aged 5-18 were studied. Main outcome measures were: BMDoc measured by peripheral DXA, total BMD measured by whole body axial scanner, age, anthropometry, pubertal status, self-reported fracture history, and physical activity (PA) expressed as a three point score. RESULTS: Complete data were available on 171 girls and 123 boys free of a history of fracture. BMDoc was related positively to age, body size, and total BMD, and could be predicted using a proportional model based on height alone (R2: 65% girls, 77% boys). Mean BMDoc appears to plateau in girls at 15 years and attain a value that concurs with the mean peak value in adult women. The 95% limits of agreement in repeated measures were -0.029 to 0.029 g/cm2 (n = 53). Compared with sedentary children, those doing regular sports or PA for more than five hours a week had an increased BMDoc (by about 0.03 g/cm2 or about 7% of the overall mean). A history of fracture (n = 81) was associated with a reduced BMDoc in boys but not in girls, though our study may have been underpowered for a subgroup analysis. CONCLUSIONS: BMDoc can be measured easily and quickly in children older than 5 years and provides an objective measure of areal bone density for clinical and research studies using a reference range derived from its relation to height.

The relationship between lean body mass and bone mineral content in paediatric health and disease.

INTRODUCTION: The correct interpretation of DXA data is critical to the diagnosis and management of children with suspected bone disease. This study examines the various influences on bone mineral content (BMC), as measured by dual-energy X-ray absorptiometry (DXA). MATERIALS AND METHODS: Six hundred and forty-six healthy school children and forty-three children with chronic diseases, aged 5-18 years, had their lumbar spine and whole body measured using a Lunar DPX-L DXA scanner. RESULTS: Stepwise linear regression identified lean body mass (LBM) as the strongest single predictor of BMC in the lumbar spine and the total body. A significant gender difference was observed in the relationship between BMC and LBM with girls having significantly more bone per unit LBM from 9 years of age in the spine and 13 years of age in the total body. To investigate the relationship between LBM and BMC in children with chronic disease, a two-stage algorithm based upon calculation of Z scores from the normative data was applied. Stage 1 assessed LBM for height and stage 2 assessed BMC for LBM. Ten children with spinal muscular atrophy had a mean LBM for height Z score of -1.8(1.4) but a mean BMC for LBM Z score of 1.2(1.3) indicating their primary abnormality was reduced muscle mass (sarcopenia) with no evidence of osteopenia. In contrast, 21 children with osteogenesis imperfecta had a mean LBM for height Z score of 0.4(1.7) but a mean BMC for LBM Z score of -2.5(1.8) indicating normal LBM for size but significantly reduced BMC for LBM (i.e. osteopenia) confirming a primary bone abnormality. A third group consisting of 12 children with low trauma fractures demonstrated little evidence of sarcopenia [mean LBM for height Z score -1.1(2.1)] but significant osteopenia [mean BMC for LBM Z score -1.9(1.5)]. CONCLUSION: The results from this study demonstrate how the relationship between height and lean body mass, and lean body mass and bone mineral content can be a useful method of diagnosing osteoporosis in children and how the relationships can be used to identify if the primary abnormality is in muscle or bone.

Acute and long-term management of patients with vertebral fractures.

Symptomatic vertebral fractures are associated with significant morbidity, excess mortality and health and social service expenditure. Up to 20% of patients with an incident vertebral fracture experience a further vertebral fracture within one year. It is therefore important that vertebral fractures are detected early, and treatment considered as soon as possible. Only a third of vertebral fractures come to medical attention, where they typically present with acute back pain, but other presentations include loss of height and increasing kyphosis. Spine X-rays should then be performed to confirm the diagnosis and exclude other pathology. Bone density measurements are not essential before starting treatment for osteoporosis in patients with low-trauma vertebral fractures, but may be useful to confirm osteoporosis when there is uncertainty about previous trauma. They may also aid in selecting the most appropriate therapy and monitoring response to treatment. Up to 30% of women and 55% of men with symptomatic vertebral crush fractures have underlying secondary osteoporosis, where treatment may lead to large increases in bone density. These conditions should therefore be sought by medical history, physical examination and appropriate investigations. The management of patients with acute vertebral fractures should include measures to reduce pain and improve mobility, as well as starting treatment for osteoporosis. Treatments have now been shown in randomized controlled trials to improve bone density and reduce the incidence of vertebral and non-vertebral fractures in patients with osteoporosis. Choice of treatment will depend on the underlying causes of bone loss, efficacy in any particular situation, cost, patient preference and the potential non-skeletal advantages and disadvantages.

Identification of women with reduced bone density at the lumbar spine and femoral neck using BMD at the os calcis.

We assessed the clinical usefulness of bone density measurements at the os calcis as a screening tool to identify patients with low bone density at the lumbar spine and femoral neck. Bone mineral density (BMD) was recorded in 443 women (mean age 60 years) referred to a bone densitometry service. Measurements were made at the lumbar spine and femoral neck using a Lunar DPXL and at the right os calcis using a Peripheral Instantaneous X-ray Imaging (PIXI) dual-energy X-ray absorptiometry system. Average T-scores derived using the manufacturer's data were: 1.59 for the lumbar spine, -1.41 for the femoral neck and -0.87 for the os calcis. The prevalence of osteoporosis using WHO criteria (T-scores of -2.5 or less) was 36% for the lumbar spine or femoral neck but only 9.7% for the os calcis. BMD of the os calcis correlated with that at the lumbar spine (r = 0.69, p < 0.001) and femoral neck (r = 0.67, p < 0.001). The area under the receiver operator characteristics curve was 0.836 (standard error 0.020) for the os calcis related to osteoporosis at the lumbar spine or femoral neck. Optimal accuracy was obtained at a T-score of < or = -1.3 (BMD 0.39 g/cm2) when the sensitivity was 69.6% (95% confidence interval 65.3, 73.9%) and specificity 82.6% (95% confidence interval 79.1, 86.1%). However, the probability of diagnosing low bone density from a given BMD at the os calcis varied by age and site scanned. Accordingly, for informing management strategies, the choice of a single cutoff BMD at the os calcis may not be appropriate and several thresholds may be adopted based on age, the site of interest (lumbar spine or femoral neck) and consideration of associated clinical features. Thus, the use of heel bone density scanners could reduce the number of axial bone density measurements required. The advantages of portability, low cost and shorter scan times should reduce the cost of detection and provide a greater opportunity for identification of women at risk of fracture.

Bone mineral changes during tibial fracture healing.

The traditional assessment of fracture healing by manipulation and viewing of radiographs is subjective and qualitative. Dual energy x-ray absorptiometry by contrast provides an accurate, precise, and minimally invasive quantitative measure of bone mineral density, a property that shows strong correlations with various mechanical properties of bone. Fourteen patients with unilateral tibial shaft fractures stabilized by external fixation were monitored with dual energy x-ray absorptiometry at monthly intervals after fracture. Fractured and contralateral unfractured bones (controls) were scanned on each occasion. Changes in mineralization with time over the whole length of the fractured bone could be seen. The most pronounced effects were visible in the area of the fracture, with a minimum recorded fracture site bone mineral density of 38 +/- 13% of contralateral values, but often more long term alterations in bone mineral density affected regions at some distance from this zone. Significantly, in four patients who had scans 5 or more months after fracture, the mineralization at the fracture site had returned to control levels, whereas bone mineral density in a region proximal to the fracture showed evidence of persisting posttraumatic osteoporosis.

A suggested methodology for the construction of national bone densitometry reference ranges: 1372 Caucasian women from four UK sites.

This paper presents a simple methodology for combining bone densitometry data from different sites in the UK, having instruments from the same manufacturer (LUNAR Radiation). Additive normalization factors were used on all data prior to inclusion in a reference database which ultimately included data on 1372 Caucasian women, aged 20-70 years, of whom 749 were post-menopausal. Reference data for spine (L2-L4) and femoral neck bone mineral density are given in tabular form as 3 year moving averages for: (1) all women; (2) perimenopausal women grouped by menopausal status; and (3) post-menopausal women with respect to years since menopause. These data may be used to construct Z-score. T-score or percentile reporting ranges and may be adopted as the core for a UK reference range.

Simultaneous bilateral tibial stress fractures in a 15-year-old milkman--a case report.

Although stress fractures are well recognized, their frequency, sequelae and complex aetiology are often under-rated. In this case report, we describe an unusual case of simultaneous bilateral stress fractures of the proximal tibial shaft in a young man, exposed to a sudden increase in unaccustomed joint loading due to his part-time occupation. The pathogenesis is discussed.

Ultrasound velocity and attenuation at different skeletal sites compared with bone mineral density measured using dual energy X-ray absorptiometry.

Measurements of ultrasound velocity were performed in the tibia in a group of 89 female subjects (mean age 50.6 years). Velocity and broadband ultrasound attenuation (BUA) measurements were performed in the os-calcis in a group of 100 male and female subjects (mean age 55.8 years). Dual energy X-ray absorptiometry (DEXA) scans were also performed on all of these subjects enabling measurements of lumbar spine and femoral neck bone mineral density (BMD) to be obtained. In two small subgroups of the above groups, each comprising 20 subjects, measurements of tibial BMD and os-calcis BMD were also performed. Tibial BMD and ultrasound velocity were found to be well correlated (r = 0.71), although both spine and femoral neck BMD were poorly correlated with ultrasound velocity in the tibia (r = 0.299 and 0.072, respectively). BUA of the os-calcis was moderately correlated with BMD at the same site (r = 0.44) and showed similar or slightly better correlations with BMD measurements of the lumbar spine and femoral neck (r = 0.410 and 0.537, respectively). Ultrasound velocity in the os-calcis was well correlated with os-calcis BMD (r = 0.729) but only moderately correlated with spine and femoral neck BMD (r = 0.470 and 0.498, respectively). This study suggests that BUA and ultrasound velocity measurements of the os-calcis are better predictors of BMD at the critical skeletal sites of the lumbar spine and femoral neck than ultrasound velocity in the tibia. Ultrasound velocity in the tibia and the os-calcis was found to be a good predictor of the BMD in the measured bone.

Dual-energy X-ray absorptiometry as a measure of healing in fractures treated by intramedullary nailing.

The conventional qualitative techniques of manual manipulation and plain radiography do not give a quantifiable measurement of healing. With internal fixation, manual manipulation is not usually possible, and conventional radiographs may not give much useful information, particularly if only a small amount of callus is formed. Dual-energy x-ray absorptiometry (DXA) provides an accurate method of quantifying the changes in bone mineral density (BMD) which occur during fracture healing. Preliminary work showed that the presence of a highly attenuating metal implant in the scan area did not affect the reliability of BMD data obtained from scans. On this basis, we have assessed the use of DXA in the clinical situation to monitor fractures treated by intramedullary nailing. Five fractures of the mid-shaft of the tibia stabilized by interlocked intramedullary nails have been monitored by DXA at monthly intervals through healing. DXA improves on radiography in giving a quantitative measure of fracture site mineralization. However, it is concluded that, because of the relatively small changes in callus BMD encountered with the rigid fixation provided by interlocked intramedullary nailing, DXA offers no significant diagnostic advantages over plain radiography.

An open access bone densitometry service: report of first year's operation.

Medical treatment of symptomatic osteoporosis is unsatisfactory. Treatment of patients with low bone density but without history of fracture includes hormone replacement therapy (HRT) which offers the prospect of reduced fracture risk. Dual energy X-ray absorptiometry (DXA) offers a safe and accurate technique available for the measurement of bone mineral density at a district general hospital level. All open access service providing densitometry measurements for general practitioners and hospital consultants was instigated at South Cleveland Hospital in February 1991. A major purpose of the service was to provide density measurements in order to 'inform' the discussion between the patient and doctor with regard to the use of anti-resorptive and other medical agents. We report our experience of operating such a service. The report analyses the main reasons for referrals. Nine hundred and thirty female subjects and 63 male subjects were scanned. The main reason for female referral were early menopause, consideration for HRT, personal history of fracture and family history of fracture--these account for 54.7% of all referrals. In men, there was a high incidence of fracture, back pain and the use of steroids given as reasons for referral. Sixty-seven per cent of patients were referred by general practitioners. Eighteen per cent of female lumbar spinal BMD values were between 1 and 2 S.D. below the Leeds normative mean and 9.0% below 2 S.D. Figures for the femoral neck were 22.0 and 9.0%.(ABSTRACT TRUNCATED AT 250 WORDS)

Rat bite fever without the bite.

The case is reported of a patient who developed an acute arthropathy, which was initially diagnosed as acute septic arthritis. The true diagnosis of rat bite fever due to Streptobacillus moniliformis was delayed because of difficulty in growing the organism, which has fastidious growth requirements. The patient had no history of rat bite, which is the usual form of transmission of this disease.