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J Compston

Publications and source records attributed to J Compston.

At least 19 recordsLinked to original sources
PubMed2005

Cross-calibration of dual-energy X-ray densitometers for a large, multi-center genetic study of osteoporosis.

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.

Absorptiometry, Photon↗
PubMed2005

Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.

BACKGROUND: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. METHODS: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. FINDINGS: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. CONCLUSION: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.

Aged↗
PubMed2001

Secondary causes of osteoporosis in men.

Important underlying causes of osteoporotic fracture in men include glucocorticoid therapy, low body weight, and reduced physical activity. Tobacco and alcohol use have been consistently identified as risk factors for vertebral fracture but there is less evidence that they contribute to hip fracture. Clinically overt hypogonadism is a strong risk factor for osteoporosis in men; however, the role of more subtle subclinical changes, as defined by biochemical criteria, remains to be established. The high comorbidity associated with osteoporosis, particularly in elderly men, contributes to fracture risk both through effects on bone mass and risk of falling. The management of osteoporosis in men includes diagnosis of and, where possible, correction of underlying contributory causes. Evidence from recent randomized controlled trials indicates that bisphosphonates are effective in the prevention of glucocorticoid-induced osteoporosis in men but the optimal criteria for selection of individuals for treatment requires further study.

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

Estrogen receptors alpha and beta are differentially expressed in developing human bone.

Estrogen plays an essential role in the development and maintenance of the skeleton; its effects are mediated via interactions with two estrogen receptor (ER) subtypes, alpha and beta. The aim of this study was to establish the cellular distribution of ERalpha and ERbeta in neonatal human rib bone. ERalpha and ERbeta immunoreactivity was seen in proliferative and prehypertrophic chondrocytes in the growth plate, with lower levels of expression in the late hypertrophic zone. Different patterns of expression of the two ERs were seen in bone. In cortical bone, intense staining for ERalpha was observed in osteoblasts and osteocytes adjacent to the periosteal-forming surface and in osteoclasts on the opposing resorbing surface. In cancellous bone, ERbeta was strongly expressed in both osteoblasts and osteocytes, whereas only low expression of ERalpha was seen in these areas. Nuclear and cytoplasmic staining for ERbeta was apparent in osteoclasts. These observations demonstrate distinct patterns of expression for the two ER subtypes in developing human bone and indicate functions in both the growth plate and mineralized bone. In the latter, ERalpha is predominantly expressed in cortical bone, whereas ERbeta shows higher levels of expression in cancellous bone.

Bone Development↗
PubMed2001

Colocalization of glucocorticoid and mineralocorticoid receptors in human bone.

Osteoporosis is a poorly understood but common complication of glucocorticoid therapy. The actions of glucocorticoids are mediated via glucocorticoid receptors (GRs), but in vitro, glucocorticoids also can bind to mineralocorticoid receptors (MRs). It is not known if MR protein is present in human bone and little is known of GR isoform expression (GRalpha and GRbeta). GR and MR protein expression and possible sites of action were investigated in neonatal rib and adult iliac crest biopsy specimens using antibodies specific for MR, GRalpha, and GRalphabeta. Colocalization [MR GRalpha] [MR GRalphabeta] was performed using fluorescent-conjugated secondary antibodies. GRalpha, GRbeta, and MR show distinct but overlapping patterns of expression, suggesting important functions for each receptor type. Osteoclasts showed no staining for GRalpha but strong staining for GRalphabeta, indicating expression of GRbeta and a specific role in addition to antagonizing the transcriptional activity of GRalpha. MR also was observed in osteoclasts and colocalized with GRalphabeta. Coexpression of MR, GRalpha, and GRalphabeta was seen in osteoblasts. Reverse-transcription-polymerase chain reaction (RT-PCR) of cultured osteoblast RNA confirmed expression of both GRalpha and GRbeta. Osteocytes stained with MR, GRalpha, and GRalphabeta antibodies but to a lesser degree than osteoblasts. In the neonatal rib cartilage, staining for GRalpha, GRalphabeta, and MR was present in approximately one-half of the resting and hypertrophic chondrocytes and in most of proliferating chondrocytes and chondrocytes within the mineralizing matrix. Identification of MR raises the possibility that the physiological and pharmacologic effects of glucocorticoids on bone may be mediated via MR as well as GR and that GRalpha, GRbeta, and MR synergize to influence corticosteroid metabolism in human bone.

Bone and Bones↗
PubMed2000

Prevention of osteoporotic fractures in post-menopausal women.

A number of pharmacological interventions are now available for the prevention of osteoporotic fractures in post-menopausal women. These include hormone replacement therapy, bisphosphonates, raloxifene, calcitonin, calcitriol and combined calcium and vitamin D. Factors influencing the positioning of these agents in clinical practice include their efficacy in preventing fractures at both the spine and the hip, tolerability, side-effects, cost and, in the case of raloxifene and hormone replacement therapy, the extra-skeletal risks and benefits of long-term treatment. The rates of onset and offset of the treatment effect are also important considerations; the observations that relatively short-term intervention produces a significant reduction in fracture risk in women with established osteoporosis, that treatment benefits are greatest in those with low bone mineral density and that the beneficial skeletal effects are not maintained after the withdrawal of treatment have resulted in a shift from long-term preventive strategies towards the targeting of high-risk individuals for intervention.

Calcitonin↗
PubMed2000

Bone structure in patients with low bone mineral density with or without vertebral fractures.

Vertebral fractures (VFX) are caused by low bone mass and microstructural deterioration of bone tissue. The latter is not well defined. We investigated bone structure in transiliac biopsy specimens from 88 volunteers. Biopsy specimens were obtained at baseline in the Multiple Outcomes of Raloxifene Evaluation trail, a prospective study in osteoporotic (BMD < or = -2.5 T score) postmenopausal women without or with VFX on standardized lateral spinal radiographs. Bone biopsy specimens were embedded in methylmethacrylate (MMA). Histomorphometry was done in 8 microns (U.S.A.) or 5 microns (Europe) Goldner stained sections. Vertebral fracture status (yes/no) was the outcome variable in logistic regression models adjusted for age and biopsy specimen origin (U.S.A. vs. Europe). Patients with and without VFX (26/62) were similar regarding age (69.2 +/- 5.2 years vs. 67.3 +/- 6.7 years), bone volume (BV/TV; 17.7 +/- 4.7% vs. 19.0 +/- 5.8%), and bone surface (BS/TV; 2.7 +/- 0.6 mm2/mm3 vs. 2.8 +/- 0.6 mm2/mm3). A lower cortical thickness (C.Th; 652 +/- 267 microns vs. 822 +/- 325 microns), total strut length (TSL; 826 +/- 226 microns/mm2 vs. 922 +/- 256 microns/mm2), node-to-loop (Nd-Lp) strut length (10.1 +/- 10.3% vs. 15.0 +/- 13.6%), together with a higher node-to-terminus (Nd-Tm) strut length (45.6 +/- 9.7% vs. 39.1 +/- 9.3%) were each associated with prevalent VFX (0.01 < p < 0.10). Differences in BV/TV did not explain these associations. In conclusion, cortical thinning and disruption of trabecular lattice are possible pathogenic mechanisms in patients with VFX.

Age Factors↗
PubMed1998

A UK Consensus Group on management of glucocorticoid-induced osteoporosis: an update.

In the UK, over 250 000 patients take continuous oral glucocorticoids (GCs), yet no more than 14% receive any therapy to prevent bone loss, a major complication of GC treatment. Bone loss is rapid, particularly in the first year, and fracture risk may double. This review, based wherever possible on clinical evidence, aims to provide easy-to-use guidance with wide applicability. A treatment algorithm is presented for adults receiving GC doses of 7.5 mg day(-1) or more for 6 months or more. General measures, e.g. alternative GCs and routes of administration, and therapeutic interventions, e.g. cyclical etidronate and hormone replacement, are recommended.

Bone Resorption↗
PubMed1998

Management of male osteoporosis: report of the UK Consensus Group.

Although osteoporosis is generally regarded as a disease of women, up to 30% of hip fractures and 20% of vertebral fractures occur in men. Risk factors for osteoporotic fractures in men include low body mass index, smoking, high alcohol consumption, corticosteroid therapy, physical inactivity, diseases that predispose to low bone mass, and conditions increasing the risk of falls. The key drugs and diseases that definitely produce a decrease in bone mineral density (BMD) and/or an increase in fracture rate in men are long-term corticosteroid use, hypogonadism, alcoholism and transplantation. Age-related bone loss may be a result of declining renal function, vitamin D deficiency, increased parathyroid hormone levels, low serum testosterone levels, low calcium intake and absorption. Osteoporosis can be diagnosed on the basis of radiological assessments of bone mass, or clinically when it becomes symptomatic. Various biochemical markers have been related to bone loss in healthy and osteoporotic men. Their use as diagnostic tools, however, needs further investigation. A practical approach would be to consider a bone density more than one SD below the age-matched mean value (Z < -1) as an indication for therapy. The treatment options for men with osteoporosis include agents to influence bone resorption or formation and specific therapy for any underlying pathological condition. Testosterone treatment increases BMD in hypogonadal men, and is most effective in those whose epiphyses have not closed completely. Bisphosphonates are the treatment of choice in idiopathic osteoporosis, with sodium fluoride and anabolic steroids to be used as alternatives.

Adult↗