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PubMed2006

Association of estrogen receptor alpha gene polymorphisms and lifestyle factors with calcaneal quantitative ultrasound and osteoporosis in postmenopausal Vietnamese women.

Genetic and lifestyle factors are important in the pathogenesis of osteoporosis. We investigated the relationships of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER-alpha) gene, lifestyle factors with speed of sound at the calcaneus (calcaneal SOS) and osteoporosis in a population-based study of 140 healthy postmenopausal women. By an analysis of covariates, women with higher copies of P or X alleles had higher calcaneal SOS compared with others (P=0.012, PP vs. pp; P=0.045, Xx vs. xx). Women with lower copies of px or higher copies of PX haplotypes had higher calcaneal SOS compared with others (P=0.021, 0 px vs. 2 px; P=0.011, 1 PX vs. 0 PX). The px and PX haplotypes, age and years since menopause were found to be independent predictors of calcaneal SOS in multiple linear regression models. Using logistic regression, we found an increased osteoporosis risk with evidence for a px haplotype dose effect (OR=2.82, 95% CI=1.50-5.31, P=0.001) and for a PX haplotype dose effect (OR=0.42, 95% CI=0.19-0.93, P=0.033). An increased educational level was associated with a reduced risk of osteoporosis (P=0.035 in the model with px, P=0.044 in the model with PX). In conclusion, the present study suggests that PvuII and XbaI polymorphims of the ER-alpha gene, age, years since menopause and educational level are associated with bone density, as assessed by calcaneal SOS, and osteoporosis in postmenopausal Vietnamese women.

Aged↗

PubMed2002

Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis.

To elucidate the pathology of osteoporosis associated with rheumatoid arthritis (RA), bone mass measurements were performed in 146 female patients with RA and compared with those in 150 age-matched female patients with osteoarthritis (OA) and postmenopausal osteoporosis (OP). Bone mineral density (BMD) was measured at the lumbar spine (L-BMD), the mid-radius (MR-BMD) and the calcaneus (C-BMD) by dual-energy X-ray absorptiometry (DXA), and at the distal radius by peripheral quantitative computed tomography (pQCT). The RA group showed significantly lower BMD at all sites, except L-BMD, than the OA group. Compared with the OP group, the RA group showed a significantly higher L-BMD but no difference at other sites. BMD in RA decreased with disease severity at all sites and lean body mass was highly correlated with L-BMD and C-BMD. Cross-sectional analysis revealed early bone loss at the distal radius and a decrease of L-BMD, MR-BMD, and C-BMD with disease duration. Longitudinal analysis showed that the annual loss of L-BMD, MR-BMD and C-BMD tended to be lower with increasing disease duration. Glucocorticoid administration had no influence on L-BMD, MR-BMD or C-BMD. We concluded that, unlike postmenopausal osteoporosis, osteoporosis associated with RA is characterised by relatively preserved bone mass in the axial bone and marked loss in the peripheral bone. The risk factors for generalised osteoporosis are a long disease duration, severity of disease, and decreased lean body mass.

Absorptiometry, Photon↗

PubMed2004

Content comparison of osteoporosis-targeted health status measures in relation to the International Classification of Functioning, Disability and Health (ICF).

The most frequently used instruments for health-related quality of life (HRQL) in patients with osteoporosis are the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) and the Osteoporosis Assessment Questionnaire (OPAQ 2.0 and OPAQ SV). Since HRQL- and International Classification of Functioning, Disability and Health (ICF)-based approaches have both strengths and weaknesses, it is expected that they will be used simultaneously in clinical practice and research. Therefore, we investigated the relationship between osteoporosis-targeted instruments and the ICF. All three selected instruments cover body functions, including pain in back and emotional functions. Sleep functions and energy are represented in the QUALEFFO-41 and OPAQ 2.0 but not in the OPAQ SV. Body structures and environmental factors are covered only by the OPAQ 2.0 and OPAQ SV. The ICF provides an excellent framework when comparing the content of osteoporosis-targeted HRQL instruments and may be useful when selecting health status instruments for clinical studies.

Activities of Daily Living↗

PubMed2006

Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis.

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis.

Absorptiometry, Photon↗

PubMed2006

Strategies for the prevention and control of osteoporosis in developing countries.

The frequency of osteoporosis and fragility fractures has been studied to a very limited extent in few developing countries. The aim of this paper is to review briefly the burden of osteoporosis and fragility fractures in these countries and to propose some strategies for the prevention and control of those conditions, considering barriers and facilitators for their implementation. The evolution of the demographic composition in most regions with developing countries shows a considerable increase in life expectancy and therefore, a significant growth in elderly population can be expected. Reports on the incidence of fragility fractures show figures in many of those countries that are comparable to those found in developed nations. Health resources (for acute treatment of fractures, their rehabilitation and chronic management, for diagnostic centers and drug therapy for osteoporosis) are limited in most of those regions and are allocated to other health priorities. Internationally accepted guidelines can be adapted to the realities of developing nations and may be promoted by organizations of health professionals and patients, but require endorsement and support by health authorities. The steps should include: (a) campaigns to increase awareness, both among the population at risk and relevant health workers; (b) the promotion of a preventive lifestyle in the general population; (c) the development of national or regional, evidence-based guidelines for the diagnosis and treatment of osteoporosis; (d) development and implementation of guidelines for the treatment of fragility fractures, their rehabilitation and prevention of falls; (e) collection of economic data on fractures and osteoporosis; and (f) development of country-specific fracture databases. These steps may help in reducing the increasing burden of osteoporotic fractures. Their implementation will require solid scientific basis and commitment from policy makers, health professionals, patient organizations, and ultimately the general population.

Developing Countries↗

PubMed2006

Genetics of osteoporosis.

Osteoporosis is a systemic skeletal disease comprising rarefaction of bone structure and loss of bone mass, finally leading to increased fracture risk. As a part of its multifactorial aetiology, twin and family studies have demonstrated an important genetic component of osteoporosis regarding many parameters of bone properties e. g. bone mineral density, with a heredity of 60-80 %. Whole genome screens, linkage analysis and candidate gene research have contributed to our current knowledge about genetic loci in osteoporosis. Genotyping of collagen alpha I, lactose intolerance or estrogen receptor alpha alleles are under investigation for their importance in individual and epidemiological practice, e. g. the European Union "GENOMOS" project with more than 50,000 subjects. In future, improved genotyping methods and design strategies as well as large scale epidemiological studies in the general population will bring the genetics of complex diseases such as osteoporosis to a point of success comparable to where mendelian genetics now firmly resides. Given the potential of these new techniques, a paradigm shift may occur both in diagnosis and prevention as well as in individualized treatment aspects of osteoporosis.

Aged↗

PubMed2006

Vertebral osteoporosis and trabecular bone quality.

Vertebral fractures due to osteoporosis commonly occur under non-traumatic loading conditions. This problem affects more than 1 in 3 women and 1 in 10 men over a lifetime. Measurement of bone mineral density (BMD) has traditionally been used as a method for diagnosis of vertebral osteoporosis. However, this method does not fully account for the influence of changes in the trabecular bone quality, such as micro-architecture, tissue properties and levels of microdamage, on the strength of the vertebra. Studies have shown that deterioration of the vertebral trabecular architecture results in a more anisotropic structure which has a greater susceptibility to fracture. Transverse trabeculae are preferentially thinned and perforated while the remaining vertical trabeculae maintain their thickness. Such a structure is likely to be more susceptible to buckling under normal compression loads and has a decreased ability to withstand unusual or off-axis loads. Changes in tissue material mechanical properties and levels of microdamage due to osteoporosis may also compromise the fracture resistance of vertebral trabecular bone. New diagnostic techniques are required which will account for the influence of these changes in bone quality. This paper reviews the influence of the trabecular architecture, tissue properties and microdamage on fracture risk for vertebral osteoporosis. The morphological characteristics of normal and osteoporotic architectures are compared and their potential influence on the strength of the vertebra is examined. The limitations of current diagnostic methods for osteoporosis are identified and areas for future research are outlined.

Animals↗

PubMed2006

Osteoporosis associated with gyrate atrophy: a case report.

Gyrate atrophy (GA) is a rare degenerative, hereditary disease characterized by markedly high serum ornithine levels resulting from the deficiency of ornithine-delta-amino transferase (OAT), a mitochondrial matrix enzyme. Hyperornithinaemia is accompanied by lysinuria and reduced lysine plasma levels in GA. Type I collagen is known to play a role in osteoporosis pathogenesis. Lysine has a role in cross ligament formation of type I collagen, a bone matrix element, and thus, in bone strength. Although the most common complaint in GA is visual problems, the disease may include muscle involvement, as well. Reduced physical activity resulting from muscle involvement and hypolysinemia in GA may lead to osteoporosis. However, there is no data in the literature concerning the relation between GA and osteoporosis. In this report a GA case with early osteoporosis, besides visual deterioration and muscular signs, is reported, and the relation between GA and osteoporosis is emphasized for the first time.

Adult↗

PubMed2006

Guidelines for the diagnosis of osteoporosis: T-scores vs fractures.

The development of bone mineral densitimometry methodologies, especially central dual energy X-ray absorptiometry (DXA) methods have allowed this quantitative tool to be used to diagnose osteoporosis before the first fragility fracture has occurred. The World Health Organization osteoporosis working group set the stage for the BMD cut-off criteria development. The wide application of DXA has brought the treatment of osteoporosis to the primary care level, a very necessary step if this increasingly prevalent disease is to have a decline in its incidence. The most difficult osteoporosis cases, for which there are many and their associated difficult DXA results and interpretation will always require specialists' involvement. In particular, the embracement of the WHO absolute fracture risk validated project will take DXA to a much greater level of value in making management decisions. In particular, the WHO absolute risk data will allow physicians, health-economic policy makers, and payors of medical services to come closer together to decide which patients are at a level of unacceptable fracture risk that justifies treatment intervention. The implementation of this validated project will also remove the unacceptable subjective computer printouts on DXA reports that often lead to the over-treatment of low risk patients and at times the under-treatment of high risk patients. The evolution of the clinical interpretation of bone densitometry has been a work in progress. Challenges in the clinical measurement of bone strength remain and will also evolve. The field of osteoporosis has grown with the use of DXA and will continue to embrace this technology as other technologies to measure fracture risk become applied in clinical practice.

Absorptiometry, Photon↗

PubMed2003

Osteoporosis and diabetes.

Osteoporosis is the most prevalent metabolic bone disease in the United States. Although the disease has historically been reported mostly in white women, it can affect individuals of both sexes and all ethnic groups. The presence of osteoporosis related to diabetes is not well acknowledged and the impact of osteoporosis in a diabetic patient is often not considered. Routine screening or initiation of preventive medications for osteoporosis in all patients with type 1 or type 2 diabetes is not recommended at the present time. However, in all patients with diabetes, besides optimal glycemic control, general recommendations regarding adequate dietary calcium intake, regular exercise, and avoidance of other potential risk factors such as smoking should be given. In patients who have positive risk factors for osteoporosis, or in those who present with fractures, evaluation of bone density should be done and respective preventive or therapeutic interventions should be applied.

Blood Glucose↗

PubMed2003

Osteoporosis in women with breast cancer.

Osteoporosis is a disease that causes substantial morbidity and mortality for which preventive therapy is available. Women with breast cancer are at increased risk for osteoporosis for several reasons, including premature ovarian failure as a result of treatment, direct effects of chemotherapy, and effects of the breast cancer itself. As the incidence of breast cancer continues to increase and survival rates continue to improve, the importance of appropriate screening for and management of osteoporosis becomes more apparent. This article reviews the evidence supporting an increased risk for development of osteoporosis in women with breast cancer and summarizes strategies for prevention and treatment of osteoporosis in this population.

Antineoplastic Agents↗

PubMed2005

Genetic epidemiology of osteoporosis: past, present, and future.

Research during the past several decades has unequivocally established a role of heredity in the etiology of osteoporosis. Major efforts are currently underway to identify the genes and allelic variants that confer genetic susceptibility to this common and disabling condition. Genome-wide linkage mapping in families, candidate gene association studies in unrelated individuals, and quantitative trait locus mapping in animal models are the primary strategies being used to search for the genetic contributors to osteoporosis. Genome-wide mapping efforts have identified the low-density lipoprotein receptor-related protein 5, bone morphogenetic protein 2, and 15-lipoxygenase as potential susceptibility genes for osteoporosis in the past few years, providing a rich new base for understanding bone biology. Candidate gene association analyses have also provided evidence for a modest role of allelic variants in several additional genes including collagen type Ialpha1, vitamin D receptor, and estrogen receptor-alpha. With the development of a high-density genome-wide polymorphism and haplotype map and continued improvements in high-throughput and cost-effective genotyping technologies, many more genetic contributors to osteoporosis will probably be identified in the near future. The results of this research should facilitate the development of new methods for diagnosing, preventing, and treating the growing clinical and public health problem of osteoporosis.

Animals↗

PubMed2002

The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis.

Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint. The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis.

Aged↗

PubMed1982

Postmenopausal osteoporosis. A heterogeneous disorder as assessed by histomorphometric analysis of Iliac crest bone from untreated patients.

Twenty-six women with untreated postmenopausal osteoporosis underwent iliac crest biopsy following tetracycline-labeling and mineral metabolism studies. Histomorphometric assessment of their bone remodeling rates, including formation determined by the tetracycline-labeling technique, revealed considerable variation. Eight women had no evidence of active bone formation (inactive remodeling osteoporosis), whereas the others showed a spectrum of bone formation rates (active remodeling osteoporosis). Clinical and biochemical studies failed to predict the histomorphometric findings. Postmenopausal osteoporosis is a histologically heterogeneous disorder with morphologic expression in bone that cannot be predicted by single or combined routine clinical and laboratory parameters. Bone biopsy, necessary to identify the histologic lesion and assess skeletal dynamics, may prove to be important for optimal therapy of osteoporosis, as a variety of agents--with different effects on bone remodeling--are available.

Aged↗

PubMed1987

Hormonal influences on osteoporosis.

Osteoporosis has recently received increased attention in both the medical and lay literature. It is estimated that there are more than one million osteoporosis-related fractures yearly in the United States, which are responsible for between three and four billion dollars in health care expenditures. A discussion of osteoporosis requires consideration of both the physiology and pathophysiology of bone tissue. In a structural sense, bone exists in two forms, the outer compact cortex accounting for 80 percent of total bone volume, and the more porous inner trabecular bone. Bone-forming osteoblasts and bone-resorbing osteoclasts are responsible for the ongoing, life-long process of formation and resorption of bone. Sex hormone deficiency, as well as chronic illness, malnutrition, and childhood immobilization, has deleterious effects on growth and modeling, ultimately reducing peak bone mass and setting the stage for osteoporosis in later life. Estrogen is known to have a protective effect on the female skeleton. The mechanisms of this effect are unknown, although estrogen may protect against parathyroid hormone-mediated bone loss. There may be a particular subset of postmenopausal women who are particularly susceptible to estrogen deficiency. Calcitonin levels, which decrease postmenopausally, return to normal with estrogen; other hormones may also play important roles. Osteoporosis is not the result of a single hormonal deficiency or excess; it must be considered in relation to other pathogenetic and risk factors.

Bone Marrow↗

PubMed1986

Osteoporosis and mandibular bone resorption: a prosthodontic perspective.

Previous studies have examined the effects of osteoporosis on the vertebra, femur, and tibia. However, few studies have examined the effects on the mandible by using an animal model to quantify bone resorption. Osteoporosis was induced through pair feedings of a high protein, low calcium diet. Before this induction, experimental and control animals were injected subcutaneously with radioactive tritiated tetracycline. Bone resorption was quantified by measuring the amount of radioactivity present after the test diets were given for 90 days. Standard scintillation techniques were used for extracting the radioactivity from each half mandible. The following conclusions can be made from the results of this investigation: A significant difference in mandibular bone resorption was associated with an osteoporotic inducing diet high in protein and low in calcium. Bone resorption in the experimental group of animals was 17% greater than in the control group. Alkaline phosphatase may be an important indicator of osteoporosis in the Sprague-Dawley rat. Elevated levels were found in those with the osteoporotic diet. The animals in the control and experimental groups consumed similar amounts of their respective diets. No significant difference was found in the weight gains of either group. The histologic picture, although not pathognomonic for osteoporosis, was consistent with many findings in the literature describing osteoporosis. This study has shown that osteoporotic diets may increase the amount of bone resorption in the mandibles of Sprague-Dawley rats.

Animals↗

PubMed1989

Maintained improvement in calcium balance and bone mineral content in patients with osteoporosis treated with the bisphosphonate APD.

The effects of the (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in osteoporosis were investigated in a series of open studies. Seven patients received a high dose of 600 mg/day of APD orally and showed an increase in calcium balance of 5.5 mmol/day (P less than 0.01) within a period of 10 days. In a group of 14 patients with osteoporosis, receiving a low dose of 150 mg/day of APD continuously, the mean calcium balance rose from -0.72 +/- 0.59 mmol/day before treatment to 1.33 +/- 0.87 mmol/day (P less than 0.005) after 1 year. In 24 patients treated with APD 150 mg/day for a mean period of 3.7 years (range 1.4-6.2) repeated dual photon absorptiometry measurements of the lumbar spine showed a mean rate of increase in bone mineral content of 3.1 +/- 1.0% per year (P less than 0.005). This yearly gain in bone mineral content appeared continuous for several years of treatment. In a comparable group of 19 patients with osteoporosis who also received conventional care and treatment but no APD, no significant changes in bone mineral content were found. Addition of a low dose of APD to conventional treatment of osteoporosis does not only prevent bone loss but induces a continuous gain in bone mass. These results justify long-term prospective studies with uninterrupted low dose APD treatment in osteoporosis.

Adult↗

PubMed1995

The climacteric, osteoporosis and hormone replacement; views of women aged 45-49.

We report climacteric symptoms among women aged 45-49, and their attitudes towards HRT and osteoporosis prevention. Semi-structured questionnaires were administered to 481 women attending for bone density screening after random invitation. We recorded social class, menopausal status, history of HRT exposure and climacteric symptoms, awareness of HRT and osteoporosis, and potential willingness to consider HRT before and after bone densitometry. In total, 294 (61%) were from non-manual social classes; 338 (70%) were premenopausal, 68 (14%) postmenopausal and 75 (16%) uncertain; 101 (21%) were current/previous HRT users. Three or more climacteric symptoms were experienced by 189 (56%) of premenopausal women, compared to 64 (94%) of postmenopausal women. Most women had heard of HRT (96%) and osteoporosis (84%), usually from women's magazines or friends. HRT was usually prescribed for climacteric symptoms and, in one case, for osteoporosis prevention. Side effects were reported with most HRT preparations and affected 38% of all users. Of the 380 (79%) women who had never taken HRT, half had concerns about such treatment, and few wanted it at the menopause. However, 364 (96%) said they would consider HRT if their bone scan suggested increased osteoporosis risk. In conclusion, women around the menopause experience considerable climacteric morbidity, but are often anxious about HRT use. Better health education might improve HRT uptake, while long-term compliance might be enhanced by disclosure of fracture risk.

Bone Density↗