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D J Hosking

Publications and source records attributed to D J Hosking.

At least 19 recordsLinked to original sources
PubMed2002

The management of primary hyperparathyroidism.

Recent improvements in parathyroid imaging have led to renewed interest in the criteria for, and the surgical approach to, parathyroidectomy. It therefore seemed appropriate to review current evidence relating to the evaluation and management of primary hyperparathyroidism for those working within a general endocrine service. The recommendations are based on an electronic search spanning the past decade using the search terms hyperparathyroidism, management and parathyroidectomy/surgery, but we have also included key publications outside this period. The findings have been graded systematically (Appendix), according to the quality of the information available, to indicate the level of evidence on which they are based.

Bone Density↗
PubMed2002

Management of corticosteroid-induced osteoporosis.

Corticosteroid (CS) therapy is widely used in the treatment of rheumatic diseases. Osteoporosis remains one of its major complications. The risk of low bone mineral density (BMD) and fracture may be already increased in some of the rheumatic diseases, regardless of CS therapy. However, in spite of this, preventative treatment for osteoporosis in patients on CS remains low. Patients on or about to start CS use for more than 6 months are at risk of corticosteroid-induced osteoporosis (CIOP). The pathogenesis of CIOP differs from post-menopausal osteoporosis in that bone formation is said to be more suppressed compared with bone resorption. The diagnosis of CIOP can be made on clinical risk factors and may not require measurement of BMD. Many agents used in post-menopausal osteoporosis such as activated vitamin D products, hormone replacement therapy, fluoride, calcitonin and the bisphosphonates have been shown to maintain or improve BMD in CIOP. However, there are few data on the reduction in fracture rates in CIOP, but the bisphosphonates seem the most promising in this regard.

Adrenal Cortex Hormones↗
PubMed2002

Alendronate in the treatment of primary hyperparathyroid-related osteoporosis: a 2-year study.

We investigated the effect of alendronate on calcium, PTH, and bone mineral density in 27 female and 5 male patients with primary hyperparathyroidism. The treatment group [n = 14; T score < or = -2.5 SD at the femoral neck (FN) or T < or = -1.0 SD plus previous nonvertebral fracture] was given alendronate 10 mg/d for 24 months. The second group (n = 18; T score > -2.5 SD at the FN) was untreated. Biochemistry was repeated at 1.5, 3, 6, 12, 18, and 24 months, and dual-energy x-ray absorptiometry at 12 and 24 months. There were no significant between-group baseline differences in calcium, creatinine, or PTH. Alendronate-treated patients gained bone at all sites [lumbar spine (LS), 1 yr gain, +7.3 +/- 1.7%; P < 0.001; 2 yr, +7.3 +/- 3.1%; P = 0.04). Untreated patients gained bone at the LS over 2 yr (+4.0 +/- 1.8%; P = 0.03) but lost bone elsewhere. Calcium fell nonsignificantly in the alendronate group between baseline (2.84 +/- 0.12 mmol/liter) and 6 wk (2.76 +/- 0.09 mmol/liter), with a nonsignificant rise in PTH (baseline, 103.5 +/- 14.6 ng/liter; 6 wk, 116.7 +/- 15.6 ng/liter). By 3 months, values had reverted to baseline. In primary hyperparathyroidism, alendronate is well tolerated and significantly improves bone mineral density at the LS (with lesser gains at FN and radius), especially within the first year of treatment. Short-term changes in calcium and PTH resolve by 3 months.

Absorptiometry, Photon↗
PubMed2001

Reproductive, menstrual and menopausal factors: which are associated with bone mineral density in early postmenopausal women?

The associations between a number of reproductive and menopausal factors and bone mineral density (BMD) were studied in a sample of early postmenopausal women. The study included 580 women aged 45-61 years who completed a risk factor questionnaire containing sections on obstetric and menstrual history. BMD measurements were taken at the anteroposterior (AP) spine, greater trochanter, femoral neck, total radius and whole body, along with whole body bone mineral content (BMC). In analyses adjusting for key confounders, number of pregnancies was more strongly associated with increased BMD than number of live births at all sites (p<0.05 at femoral neck and total radius), and menstrual years was more strongly associated with increased BMD than years since menopause (p<0.05 at all sites). Hysterectomized women had a significantly higher adjusted mean BMD than non-hysterectomized women at all sites (AP spine: 0.999 g/cm2 vs 0.941 g/cm2, p<0.001), although there were no significant differences in BMD between hysterectomized women who had a bilateral oophorectomy and those whose ovaries were preserved. Negative associations between the duration of hot flushes and BMD were statistically significant (p<0.05) at the three non-hip sites. In multiple regression analyses containing all reproductive terms, duration of hormone replacement therapy (HRT) use, menstrual years and hysterectomy status were significantly associated with BMD at all five sites, whilst oral contraceptive use before the age of 23 years was significantly associated with increased BMD at all sites except the total radius. Breastfeeding duration, the duration of oral contraceptive use and premenopausal amenorrhea were found to have no association with BMD. Results for whole body BMC were consistent with those for the five BMD sites, across all the variables considered here. These findings confirm the importance of HRT use and duration of menses as predictors of BMD, whilst the results for hysterectomy status and early oral contraceptive use require further consideration.

Amenorrhea↗
PubMed2001

Distal forearm fracture history in an older community-dwelling population: the Nottingham Community Osteoporosis (NOCOS) study.

OBJECTIVES: to assess the prevalence of a history of Colles' fracture (occurring after the age of 40 years) and to ascertain the extent of investigation and treatment of osteoporosis in this population. METHODS: we studied subjects aged > or =60 years from the age-sex register of three general practices. We recorded a history of fractures and details of any previous investigation for osteoporosis and treatment with bone-protective drugs. Bone mineral density was performed at the heel using dual-energy x-ray absorptiometry (Lunar PIXI machine). We classified subjects into normal, osteopaenic or osteoporotic according to the machine manufacturer's recommended World Health Organisation 'equivalent T-score thresholds' (0.6 for osteopaenia and 1.6 for osteoporosis). RESULTS: of the 605 subjects invited, we recruited 259 women and 194 men (response rate=74.8%). Twenty-eight (10.8%) of the women and five (2.6%) of the men had a history of Colles' fracture. Of women with a prevalent Colles' fracture, 39% were osteoporotic and 36% were osteopaenic. These rates were significantly greater than in women without a Colles' fracture (19.9% osteoporotic, 29.4% osteopaenic; P=0.018). Assuming the same PIXI thresholds for men, two (40%) of the five men with a history of Colles' fractures were osteoporotic and the rest were osteopaenic, compared with 20.6 and 31.2% of men without a history of Colles' fractures. None of the subjects in the Colles' fracture group had previously been investigated with bone densitometry. Women with and without a history of Colles' fracture did not differ significantly in ever having (32.1% vs 27.2%; P=0.4) or currently having (14.3% vs 10.4%; P=0.4) hormone replacement treatment. None of the men and only one woman with a previous Colles' fracture had ever taken a non-hormone replacement treatment for osteoporosis. CONCLUSIONS: older community-dwelling subjects with previous Colles' fracture have a high prevalence of osteoporosis and are under-investigated and under-treated. Methods for identifying subjects with a previous Colles' fracture need to be developed in primary and secondary care.

Aged↗
PubMed2001

Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study.

BACKGROUND: calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss, with an enhanced risk of osteoporotic fractures. Although hip fractures are a serious consequence, few therapeutic measures are given for primary or secondary prevention. A combination of calcium and vitamin D may not be the most effective treatment for all patients. OBJECTIVE: to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis, bone mineral density and fracture type, and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients. DESIGN: a population-based, prospective cohort study. METHODS: 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture. This ward accepts people who live at home and are independent in activities of daily living. All subjects had a baseline medical examination, biochemical tests (parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) and were referred for bone densitometry. RESULTS: at 68%, the prevalence of hypovitaminosis D (25-hydroxyvitamin D<30 nmol/l) was high. However, only half the patients had evidence of secondary hyperparathyroidism, the rest having a low to normal level of parathyroid hormone ('functional hypoparathyroidism'). Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium, higher 1,25-dihydroxyvitamin D, lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the 'functional hypoparathyroid' group (P<0.01). CONCLUSION: there is a high prevalence of hypovitaminosis D in active, elderly people living at home who present with a hip fracture. However, secondary hyperparathyroidism occurs in only half of these patients. This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover, leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures. Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients, but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and 'vitamin D-replete' subjects needs further evaluation.

Aged↗
PubMed2001

Secondary prevention of osteoporosis: when should a non-vertebral fracture be a trigger for action?

The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

Accidental Falls↗
PubMed2001

The use of a whole body index with bone scintigraphy to monitor the response to therapy in Paget's disease.

Bone scintigraphy has long been used to assess Paget's disease and investigate the response to therapy. Objective visual assessment is, however, difficult. The aim of this study was to derive, from a bone scintigram, an index which objectively measured the extent and severity of Paget's disease in the entire skeleton. This whole body index would provide a single numerical value which could be used to monitor the response to therapy in both monostotic and polyostotic disease. Comparison with other methods of assessing the condition, such as biochemical markers and pain scores, would also be possible. The whole body index was developed and used to retrospectively analyse 80 bone scintigrams on 40 patients. The majority of patients (36) received treatment with a bisphosphonate between the two scintigrams. Whole body index was compared with serum alkaline phosphatase measured at the same time; a significant correlation was found (before treatment P=0.001, after treatment P<0.001). The change in whole body index and alkaline phosphatase following treatment with various bisphosphonates was also investigated and a significant correlation found (P<0.001). Whilst performing the analysis it was also noted that the increase in uptake of the radiopharmaceutical was significantly greater in the cortical long bones than in the trabecular axial skeleton. This study suggests that a whole body index may be a suitable tool for assessing the response to treatment in Paget's disease.

Aged↗
PubMed2001

The contribution of nutritional factors to osteopenia in the elderly.

Calcium and vitamin D deficiency increase age-related bone loss by causing secondary hyperparathyroidism. Reduced endogenous vitamin D synthesis exacerbates the problem of dietary deficiency and involves elderly people living in their own homes, who are just as much at risk as those living in institutionalized care. The effects of secondary hyperparathyroidism may be offset by hypercalcaemia of the increased bone turnover of immobility, which has a direct adverse effect on the skeleton causing osteoporosis. Active vitamin D analogues are effective in suppressing secondary hyperparathyroidism caused by vitamin D deficiency. However, simple deficiency is optimally treated with parent vitamin D, which has a greater safety margin than active vitamin D therapy (1,25 dihydroxyvitamin D), which requires close monitoring in the elderly.

Aged↗
PubMed2000

A comparison of the longitudinal changes in quantitative ultrasound with dual-energy X-ray absorptiometry: the four-year effects of hormone replacement therapy.

Quantitative ultrasound (QUS) has been proposed as a tool which can measure both the quantitative and qualitative aspects of bone tissue and can predict the future risk of osteoporotic fractures. However, the usefulness of QUS in long-term monitoring has yet to be defined. We studied a group of early postmenopausal women over a 4-year period. Thirty subjects were allocated to hormone replacement therapy and 30 selected as controls matched for age, years past the menopause (YPM) and bone mineral density (BMD) at the anteroposterior spine (AP spine). The mean age of the subjects was 52.4 years (SD 3.9 years), mean YPM 4.0 years (SD 3.2) and all subjects had a BMD T-score above -2.5 SD (number of standard units related to the young normal mean population). BMD was measured at baseline and annually by dual-energy X-ray absorptiometry (DXA) at the AP spine and total hip, and QUS carried out at the calcaneus, measuring broadband ultrasound attenuation (BUA), speed of sound (SOS) and Stiffness. Mean percentage changes from baseline were assessed at 2 and 4 years. The overall treatment effect (defined as the difference in percentage change between the two groups) was: AP spine BMD, 11.4%; total hip BMD, 7.4%; BUA, 6.4%; SOS, 1.1%; and Stiffness, 10.4% (p<0.01). To compare the long-term precision of the two techniques we calculated the Standardized Precision, which for QUS was approximately 2-3 times that of DXA, for a given rate of change. The ability of each site to monitor response to treatment was assessed by calculating the Treatment Response Index (Treatment Effect/Standardized Precision), which was: AP spine BMD, 10.4; total hip BMD, 3.9; BUA, 3.1; SOS, 0.3; and Stiffness, 4.2. This was then normalized for AP spine BMD (to compare the role of QUS against the current standard, AP Spine BMD), which was: total hip BMD, 0.38; BUA, 0.30; Stiffness, 0.40 (p<0.01); and SOS, 0.03 (NS). In summary, QUS parameters in the early menopause showed a similar rate of decline as AP spine BMD and total hip BMD measured by DXA. Hormone replacement therapy results in bone gain at the AP spine and total hip, and prevents loss in BUA and SOS measured by QUS at the calcaneus. QUS has a potential role in long-term monitoring, although presently the time period to follow individual subjects remains 2-3 times that for DXA, for a given rate of change. Anteroposterior spine remains the current optimal DXA monitoring site due to its greater rate of change and better long-term precision.

Absorptiometry, Photon↗
PubMed2000

A comparison of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in the treatment of postmenopausal vertebral osteoporosis: a randomized controlled trial.

A number of drugs are now available for the treatment of established osteoporosis and have been shown to significantly increase bone mineral density (BMD). There are, however, few comparative treatment studies and, furthermore, adverse events remain a problem with some of the newer agents, particularly in the elderly, in everyday clinical practice. We report a 12 month, open labeled, randomized controlled, prospective treatment study in 140 postmenopausal women with established vertebral osteoporosis, comparing the effect of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in terms of gain in BMD, reduction in bone turnover markers and adverse event profile. The mean percentage increases in BMD at 12 months, at the spine and hip respectively, were: continuous alendronate 5.7%, 2.6%; cyclical alendronate 4.1%, 1.6%; cyclical etidronate 4.9%, 2.0% (p<0.0 1) and calcitriol 2.0%, 0.4% (NS). In comparison with calcitriol, the mean changes in BMD at the spine and hip respectively were greater in the other groups; continuous alendronate: 3.7% (95% CI 1.4 to 8.3), 2.2% (95% CI 0.7 to 4.0); cyclical alendronate: 2.1% (95% CI 1.2 to 6.4), 1.2% (95% CI -0.3 to 3.0); cyclical etidronate: 2.9% (95% CI 1.9 to 6.5), 1.6% (95% CI 0.9 to 3.1)). The reduction in bone turnover markers was between 26% and 32% in the alendronate and etidronate groups (p<0.01), with a trend toward greater reduction in the continuous alendronate group. Eight patients discontinued the study: 6 in the continuous alendronate group, 1 in the cyclical alendronate group and 1 in the calcitriol group. Two patients in the cyclical etidronate group were unable to tolerate the Cacit component, but continued on substituting Cacit with Calcichew. In summary, 12 months of treatment with continuous alendronate, cyclical alendronate and cyclical etidronate are effective in terms of the gain in BMD at the anteroposterior spine and total hip in a comparable treatment population. These treatments are more effective than calcitriol and were generally well tolerated. Continuous alendronate showed a trend toward a larger gain in BMD and greater suppression of bone turnover markers than the other treatment groups, but had a higher incidence of adverse events, particularly within the older subgroup. Cyclical alendronate offers a lower adverse event profile and appears to be effective in comparison with continuous treatment, and may possibly be an alternative in the elderly. However, further studies are necessary, but more importantly with fracture end-points.

Administration, Oral↗
PubMed2000

Site-specific variation in the classification of osteoporosis, and the diagnostic reclassification using the lowest individual lumbar vertebra T-score compared with the L1-L4 mean, in early postmenopausal women.

In this study we report first the concordance and variation in diagnostic osteoporosis classification using multiple skeletal site measurements compared with the lumbar spine only; and secondly, at the lumbar spine, the variation and diagnostic osteoporosis reclassification using the lowest individual vertebra T-score compared with the L1-L4 mean T-score. One hundred and fifty early postmenopausal women were evaluated as part of the recruitment for a multicenter osteoporosis prevention study. Bone mineral density (BMD) was restricted such that no more than 10% of the subjects had a lumbar spine BMD below 0.8 g/cm2. Forty-seven per cent of the subjects were classified as having low bone mass (T-score < or = -1.0) at the lumbar spine, 63% at the mid-forearm, 39% at the distal forearm and 50% at the hip (p < 0.05). The greatest proportion of subjects were categorized as osteoporotic at the lumbar spine, followed by the forearm and then the hip. Correlation between sites ranged from 0.57 to 0.60 (p < 0.01). Eighty-one percent of the subjects had a significant difference between their highest and lowest individual lumbar vertebra T-score (defined as a difference outside the 90% confidence interval coefficient of variation T-score value). Using the lowest individual lumbar T-score, recategorized 33% of the subjects classified as osteopenic (based on the mean L1-L4 T-score) as osteoporotic, and 23% of those classified as normal as osteopenic (p < 0.05). Of all four vertebrae, L2 had the highest T-score in 37.7% of the subjects (mean -0.3) and L4 the lowest in 61% (mean -1.5) (mean difference 1.2 units, 95% CI 0.7 to 1.7). The classification of osteoporosis varies according to skeletal site, with pronounced differences in the early menopausal population. T-scores are useful for characterizing subjects with the highest risk of osteoporosis but BMD and fracture risk must be recognized in a continuum. Individual T-scores of the lumbar vertebrae show wide variation in the absence of degenerative spinal disease or vertebral collapse and the use of the lowest, significantly different, individual lumbar vertebra T-score reclassified over half of the subjects in this study. This poses a great therapeutic dilemma in clinical practice, particularly if these fractures are at higher risk of future collapse.

Bone Density↗
PubMed2000

Occupational activity and bone mineral density in postmenopausal women in England.

Few studies have assessed the relationship between occupational activity and bone mineral density (BMD), although two case-control studies have reported a protective effect of occupational activity on hip fracture. In the present study 580 postmenopausal women aged 45-61 years completed a risk factor questionnaire including a detailed occupational history. For each job, hours spent sitting, standing, walking, lifting and carrying were recorded; these measures, evaluated at ages 20, 30, 40 years, in the current job and over the working lifetime, were used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and measurements at five sites were used in a multiple regression analysis adjusting for potential confounding variables. There was a significant negative association between sitting at age 20 years and BMD at the radius (p = 0.037), with negative relationships of borderline significance at the anteroposterior spine (p = 0.091) and whole body (p = 0.078). There were significant positive associations between standing at age 30 years and BMD at all five sites (p < 0.05), but no significant linear associations for standing at ages 20 and 40 years. No significant associations were found for lifetime or current occupational measures of sitting, standing, walking and lifting or carrying. The lack of consistency of these significant findings suggests that they may have occurred by chance, and that occupational activity has little if any effect on BMD in postmenopausal women.

Adult↗
PubMed2000

Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy.

Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500-1000 mg), and most also received supplemental vitamin D (400 IU). The primary endpoint was the difference between the placebo and active groups in lumbar spine bone mineral density (BMD) at 1 year; changes in BMD at other sites, biochemical markers of bone turnover, and the incidence of vertebral fractures were also assessed. In the overall population, the mean (SE) lumbar spine BMD increased 1.9 +/- 0.38% from baseline in the risedronate 5 mg group (P < 0.001) and decreased 1.0 +/- 0.4% in the placebo group (P = 0. 005). BMD at the femoral neck, trochanter, and distal radius increased or was maintained with risedronate 5 mg treatment, but decreased in the placebo group. Midshaft radius BMD did not change significantly in either treatment group. The difference in BMD between the risedronate 5 mg and placebo groups was significant at all skeletal sites (P < 0.05) except the midshaft radius at 1 year. The 2.5 mg dose also had a positive effect on BMD, although of a lesser magnitude than that seen with risedronate 5 mg. A significant reduction of 70% in vertebral fracture risk was observed in the risedronate 5 mg group compared with the placebo group (P = 0.01). Risedronate was efficacious in both men and women, irrespective of underlying disease and duration of corticosteroid therapy, and had a favorable safety profile, with a similar incidence of upper gastrointestinal adverse events in the placebo and active treatment groups. Daily treatment with risedronate 5 mg significantly increases BMD and decreases vertebral fracture risk in patients receiving moderate-to-high doses of corticosteroid therapy.

Absorptiometry, Photon↗
PubMed2000

An audit of current clinical practice in the management of osteoporosis in Nottingham.

BACKGROUND: Osteoporosis is now recognized by the World Health Organization and the Department of Health as a major public health problem. In 1994, the Advisory Group on Osteoporosis (AGO), set up by the Department of Health, recommended that Health Authorities and general practitioner fundholders should purchase bone densitometry services for the management of osteoporosis. The aims of this study were to assess the criteria for requests for bone densitometry from primary care in comparison with the AGO recommendations and to compare the numbers of patients referred with a low-trauma osteoporotic fracture with the expected number of fractures in the Nottingham area. METHODS: Patient referral data and requests for bone densitometry were collected by case note review of all new patients referred to the Nottingham Osteoporosis Clinic over a 12 month period and then compared with the AGO recommendations. The patients referred with a history of a low-trauma fracture were then compared with the expected incidence of fractures, calculated using age-sex-specific fracture incidence data applied to the Nottingham population Census statistics. RESULTS: A total of 413 patients were referred to the Osteoporosis Clinic for bone densitometry. Almost two-thirds of the patients had no clinical indicators for requests for scanning, in comparison with the AGO recommendations. Seventy-seven patients were referred with vertebral fracture, 12 hip, 20 colles and 26 other fractures. Using age-sex-specific fracture incidence data applied to the Nottingham population Census statistics, it was estimated that the expected incidence of hip fractures would be 812, distal forearm fractures 514 and vertebral fractures presenting to clinical attention 625. This represents 1.5 per cent of the total hip fractures, 3.9 per cent distal forearm and 12.3 per cent vertebral actually presenting to the Osteoporosis Clinic. CONCLUSION: Bone densitometry was requested in up to 60 per cent of the patients with no clinical risk factors to warrant bone densitometry. Osteoporosis-related fractures remain unrecognized in clinical practice. The majority of patients do not receive specialist assessment despite being at high risk of future fracture. Further steps are necessary to educate health care professionals in primary and secondary care, but more importantly, to direct services more proactively in those at high risk of future fracture.

Absorptiometry, Photon↗
PubMed1999

Risedronate, a highly effective, short-term oral treatment for Paget's disease: a dose-response study.

Risedronate is a potent pyridinyl bisphosphonate being developed for bone diseases such as Paget's disease and osteoporosis. In this study, we compared the efficacy, safety, and tolerability of three different doses of oral risedronate in 62 patients with severe Paget's disease of bone [serum alkaline phosphatase (AP) >3 times the upper limit of normal]. Patients were treated at six study centers with either 10, 20, or 30 mg oral risedronate daily for 28 days and followed up to day 85. The primary efficacy parameter was percentage change from baseline in AP excess. The data show that there is a dose-response with risedronate: patients who received 30 mg oral risedronate for 28 days benefited most, with a mean percentage decrease in AP excess of 72.2% (20 mg: 57.9%; 10 mg: 48. 0%). Time to response-the first time point when there was a >/=30% reduction from baseline in AP excess and >/=50% reduction from baseline in urinary hydroxyproline (HP)/creatinine-was also significantly shorter (median 29 days) in the 30 mg group compared with the other two groups (20 mg: 43 days and 10 mg: 71 days). Long-term follow-up data up to 33 months from the start of the study indicated that AP remained below baseline levels for all patients. Histologic evaluation of bone formed during risedronate therapy demonstrated that normal lamellar bone was formed as opposed to woven pagetic bone, with no evidence of osteomalacia. Risedronate was well tolerated. Transient decreases in serum calcium and increases in serum intact parathyroid hormone were observed, consistent with the pharmacology of risedronate. In conclusion, risedronate administered at daily doses of 10, 20, and 30 mg for 28 days was effective in reducing the biochemical indices of disease activity in patients with severe Paget's disease of bone. A daily dose of 30 mg was most effective without compromising safety or tolerability.

Administration, Oral↗
PubMed1999

Association between a family history of fractures and bone mineral density in early postmenopausal women.

The aim of this analysis was to measure the strength of the association between a family history of fractures and bone mineral density (BMD), and to determine what definition of family fracture history best predicts BMD. Five hundred and eighty postmenopausal women aged 45-59 at recruitment completed a risk factor questionnaire. Women were asked to recall details of fractures sustained by any female relative. BMD measurements taken at five sites were used. The data were analysed using linear regression, adjusting for age. Two hundred and ninety-seven (52.8%) women reported a family history of fractures, and they had a significantly lower BMD at two of the sites measured (p < 0.05). The associations with BMD were most significant when only counting fractures that occurred in the subject's mother or a sister as a result of low trauma, with no restrictions made on age at the time of fracture and site of fracture (p < 0.01 at three sites; 0.01 < p < 0.05 at two sites). Women with a family history according to this definition had a 4.6% reduction in BMD at the femoral neck. When T scores were used to categorize women as either osteopenic/osteoporotic (T < -1) or normal at the femoral neck, the sensitivity of using this definition was 39% and the specificity was 74%. The small group of women that reported a low-trauma hip fracture in a mother or sister (n = 23) had a mean femoral neck BMD which was 8.9% lower than that of the remainder of the sample, although this difference was less statistically significant than when low trauma fractures at any site were counted. Of these 23 women, 70% were osteopenic or osteoporotic, compared with 57% of those reporting a low-trauma fracture at any site and 47% of the sample as a whole. The sensitivity of this definition, however, was low (6%). From these analyses it can be concluded that the definition of family fracture history that best predicts BMD in postmenopausal women is a fracture at any age in a mother or sister resulting from low trauma, although the sensitivity and specificity of using a family history of fractures by itself to screen for low BMD were poor.

Absorptiometry, Photon↗