Osteoporosis: Boonen S

Bergmann P, Body JJ, Boonen S, Boutsen Y, Devogelaer JP, Goemaere S, Kaufman JM, Reginster JY, Gangji V, Anonymous00023. · Laboratory of Clinical Chemistry, CHU Brugmann, Université Libre de Bruxelles, Bruxelles, Belgium. · Int J Clin Pract. · Pubmed #19125989 links to  free full text

Abstract: OBJECTIVES: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency. METHODOLOGY: Consensus meeting generating guidelines for clinical practice after review and discussion of the randomised controlled trials or meta-analyses on the management of osteoporosis in postmenopausal women. RESULTS: Although the correlation between BMD and BTM is statistically significant, BTM cannot be used as predictive markers of BMD in an individual patient. Both are independent predictors of fracture risk, but BTM can only be used as an additional risk factor in the decision to treat. Current data do not support the use of BTM to select the optimal treatment. However, they can be used to monitor treatment efficiency before BMD changes can be evaluated. Early changes in BTM can be used to measure the clinical efficacy of an anti-resorptive treatment and to reinforce patient compliance. DISCUSSION: Determining a threshold of BTM reflecting an optimal long-term effect is not obvious. The objective should be the return to the premenopausal range and/or a decrease at least equal to the least significant change (30%). Preanalytical and analytical variability of BTM is an important limitation to their use. Serum C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen 1 N terminal extension peptide and bone specific alkaline phosphatase (BSALP) appear to be the most suitable. Conclusion: Consensus regarding the use of BTM resulted in guidelines for clinical practice. BMD determines the indication to treat osteoporosis. BTM reflect treatment efficiency and can be used to motivate patients to persist with their medication.

Devogelaer JP, Goemaere S, Boonen S, Body JJ, Kaufman JM, Reginster JY, Rozenberg S, Boutsen Y. · Rheumatology Unit, Saint-Luc University Hospital, Université catholique de Louvain, Brussels, Belgium. · Osteoporos Int. · Pubmed #16217586 No free full text.

Abstract: Glucocorticoids (GCs) are frequently prescribed for various inflammatory and/or life-threatening conditions concerning many systems in the body. However, they can provoke many aftereffects, of which osteoporosis (OP) is one of the most crippling complications, with its host of fractures. The dramatic increase in bone fragility is mainly attributable to the GC-induced rapid bone loss in all skeletal compartments. We have reviewed the meta-analyses and randomized controlled studies reporting medical therapeutic interventions currently registered in Belgium for the management of GC-OP comparatively with a placebo. Based on this research, an expert meeting developed a consensus on the prevention and therapy of GC-OP. The pathophysiology of GC-OP is complex. Several factors, acting separately or synergistically, have been described. Their great number could help to understand the rapidity of bone loss and of bone fragility occurrence, indicating that a rapid therapeutic intervention should be implemented to avoid complications. All patients on GCs are threatened with OP, so the prevention and/or therapy of GC-OP should be considered not only for postmenopausal females, but also for osteopenic premenopausal females and for males put on a daily dose of at least 7.5 mg equivalent prednisolone that is expected to last at least 3 months. Non-pharmacological interventions, such as exercise and avoidance of tobacco and alcohol, should be recommended, even if their role is not definitely settled in GC-OP prevention. Supplemental calcium and vitamin D should be considered as the first-line therapy because of the decrease in intestinal calcium absorption provoked by GCs. They also could be considered either as isolated therapy in patients taking less than 7.5 mg prednisolone daily and/or for a predicted period shorter than 3 months or as adjuvant therapy to other more potent drugs. Hormone replacement therapy could be considered in young postmenopausal females on GC, such as in postmenopausal OP, or in men with low androgen levels. Calcitonin appears to have a protective effect on trabecular bone in GC-OP, just as in postmenopausal OP. There is an increasing body of evidence supporting the antifracture efficacy of bisphosphonates, notably alendronate and risedronate. Preventative and curative therapy of GC-OP should be maintained as long as the patient is on GC treatment and could be stopped after weaning from GC, because there is more than circumstantial evidence of some recovery of BMD when GCs are stopped. There is no indication in GC-OP for any combination of two antiresorptive agents (except for calcium and vitamin D) or for an antiresorptive and an anabolic agent. There is indeed no proof that the increased costs of combined treatments will translate into increased therapeutic efficacy.

Boonen S, Body JJ, Boutsen Y, Devogelaer JP, Goemaere S, Kaufman JM, Rozenberg S, Reginster JY. · Center for Metabolic Bone Diseases, Katholieke University Leuven, Leuven, Belgium. · Osteoporos Int. · Pubmed #15726235 No free full text.

This publication has no abstract.

Boonen S, Crepaldi G. · No affiliation provided · Aging Clin Exp Res. · Pubmed #17332714 No free full text.

This publication has no abstract.

Boonen S, Dejaeger E, Vanderschueren D, Venken K, Bogaerts A, Verschueren S, Milisen K. · Leuven University Centre for Metabolic Bone Disease and Division of Geriatric Medicine, UZ Leuven campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. · Best Pract Res Clin Endocrinol Metab. · Pubmed #19028356 No free full text.

Abstract: Age is a major determinant of osteoporosis, but the elderly are rarely assessed and often remain untreated for this condition. Falls, co-morbidities and co-medications compound the risk of fracture in senile osteoporosis. The prevalence of osteoporosis is expected to increase with increasing life expectancy, and the associated fractures - particularly hip fractures - will lead to significant demands on health resources. Treatment of senile osteoporosis can include pharmacological and non-pharmacological intervention. Calcium and vitamin D dietary supplementation is a relatively low-cost way of reducing the risk of fracture. Pharmacological interventions with risedronate, zoledronic acid, or teriparatide have been shown to reduce vertebral fracture risk in osteoporosis patients over the age of 75. Zoledronic acid has been shown to reduce fracture risk in frail patients with recent hip fracture. In the oldest old (patients over 80), strontium ranelate is the first agent with documented anti-fracture efficacy for both non-vertebral and vertebral fracture and documented sustained efficacy over 5 years. Falls prevention is an essential component of any strategy for decreasing fracture risk in old age. Currently, senile osteoporosis is under-diagnosed and under-treated, but age should not be a barrier to intervention.

Boonen S, Vanderschueren D, Venken K, Milisen K, Delforge M, Haentjens P. · Leuven University, Department of Experimental Medicine, Leuven, Belgium. · J Intern Med. · Pubmed #18823505 No free full text.

Abstract: Bisphosphonates are the current mainstay of treatment for postmenopausal osteoporosis. Although daily oral dosing is effective, it is associated with poor compliance, partly because of the pre and postdose fasting and posture requirements. This negatively impacts treatment outcomes, leading to a reduced clinical benefit. Improved, yet still suboptimal adherence has been noticed with less frequent bisphosphonate dosing e.g. once-weekly and once-monthly oral regimens. The recently approved quarterly intravenous (i.v.) injection regimen of ibandronate and yearly i.v. infusion of zoledronic acid are attractive options in the management of postmenopausal osteoporosis. These regimens may assure quarterly and year long compliance.

Bruyere O, Brandi ML, Burlet N, Harvey N, Lyritis G, Minne H, Boonen S, Reginster JY, Rizzoli R, Akesson K. · Department of Public Health, Epidemiology & Health Economics, University of Liège, Liège, Belgium. · Curr Med Res Opin. · Pubmed #18759997 No free full text.

Abstract: BACKGROUND: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval. METHODS: A literature search on post-fracture management of patients with hip fracture was performed on the Medline database. Key experts convened to develop a consensus document. FINDINGS: Management of hip-fracture patients to optimize outcome after hospital discharge requires several stages of care co-ordinated by a multidisciplinary team from before admission through to discharge. Further studies that specifically assess prevention and post-fracture management of hip fracture are needed, as only one study to date has assessed an osteoporosis medication in patients with a recent hip fracture. Proper nutrition is vital to assist bone repair and prevent further falls, particularly in malnourished patients. Vitamin D, calcium and protein supplementation is associated with an increase in hip BMD and reduction in falls. Rehabilitation is essential to improve functional disabilities and survival rates. Fall prevention and functional recovery strategies should include patient education and training to improve balance and increase muscle strength and mobility. Appropriate management can prevent further fractures and it is critical that high-risk patients are identified and treated. To foster this process, clinical pathways have been established to support orthopaedic surgeons. CONCLUSION: Although hip fracture is generally associated with poor outcomes, appropriate management can ensure optimal recovery and survival, and should be prioritized after a hip fracture to avoid deterioration of health and prevent subsequent fracture.

Singer AJ, Boonen S. · Georgetown University Medical Center, Washington, DC, USA. · Curr Med Res Opin. · Pubmed #18559165 No free full text.

Abstract: BACKGROUND: Osteoporosis is a prevalent disease with substantial individual and socioeconomic consequences. The challenges faced by physicians include identifying individuals at high risk of fracture, selecting the optimal treatment plan for each patient, and educating patients regarding their role in the effectiveness of therapy. SCOPE: This article discusses screening and patient selection for osteoporosis treatment, as well as available bisphosphonate therapies. Data on patient adherence and cost-effectiveness are also reviewed. The aim is to raise awareness among clinicians of the importance of osteoporosis assessment and of the differences in clinical outcomes between therapies. FINDINGS: Reviewed data indicates that risk-factor assessment is invaluable in diagnosing osteoporosis and guidelines are available which should be consulted to help determine which patients need treatment. When selecting a treatment plan, the differences between therapies in terms of vertebral and nonvertebral efficacy, timing of onset of action, and tolerability should be considered. Furthermore, patient adherence to a particular therapy will affect its effectiveness and can be improved through active patient education. Finally, given the large number of affected individuals, cost-effectiveness of therapies should be considered. CONCLUSION: The appropriate therapy should match individual patient needs in terms of efficacy, early onset of action, tolerability, and likelihood of patient adherence to treatment.

Boonen S, Singer AJ. · Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, Leuven, Belgium. · Curr Med Res Opin. · Pubmed #18489813 No free full text.

Abstract: BACKGROUND: Osteoporosis is a major and costly global public health problem. It is a chronic disease in which fracture is the main outcome, and the impact of these fractures can vary depending on the age of the individual and the severity of the fracture. SCOPE: Using literature review, this paper discusses and summarizes the information available regarding the individual and socio-economic consequences associated with the several types of osteoporotic fractures. FINDINGS: Different types of osteoporotic fractures are generally associated with different age groups. The health-economic impact of vertebral and hip fractures has been extensively explored and it is well known that these fractures are associated with morbidity/disability and increased mortality; they also account for a substantial portion of the direct fracture costs. However, to accurately estimate the individual and socio-economic burden of the disease, further research is needed on the morbidity/disability, mortality, and costs associated with non-hip, nonvertebral fractures, which account for more than half of the total fractures. More data are also required on the indirect costs associated with all fracture types. CONCLUSIONS: Understanding the socio-economic consequences of each fracture type will be important to fully estimate the burden of osteoporosis and may help clinicians tailor management plans for individual patients.

Venken K, Callewaert F, Boonen S, Vanderschueren D. · Bone Research Unit, Laboratory for Experimental Medicine and Endocrinology, Department of Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, Box 902, B-3000, Leuven, Belgium. · Osteoporos Int. · Pubmed #18392663 No free full text.

Abstract: Sex steroids regulate skeletal maturation and preservation in both men and women, as already recognized in the 1940s by Albright and Reifenstein. The impact of gonadal insufficiency on skeletal integrity has been widely recognized in adult men and women ever since. In the context of their skeletal actions, androgens and estrogens are no longer considered as just male and female hormones, respectively. Androgens can be converted into estrogens within the gonads and peripheral tissues and both are present in men and women, albeit in different concentrations. In the late 1980s, sex steroid receptors were discovered in bone cells. However, the understanding of sex steroid receptor activation and translation into biological skeletal actions is still incomplete. Due to the complex metabolism, sex steroids may have not only endocrine but also paracrine and/or autocrine actions. Also, circulating sex steroid concentrations do not necessarily reflect their biological activity due to strong binding to sex hormone binding globulin (SHBG). Finally, sex steroid signaling may include genomic and non-genomic effects in bone and non-bone cells. This review will focus on our current understanding of gonadal steroid metabolism, receptor activation, and their most relevant cellular and biological actions on bone.

Body JJ, Bergmann P, Boonen S, Boutsen Y, Devogelaer JP, Goemaere S, Reginster JY, Rozenberg S, Kaufman JM. · Department of Medicine, CHU Brugmann and Institute J Bordet, Université Libre de Bruxelles, 4 place van Gehuchten, Brussels 1020, Belgium. · Osteoporos Int. · Pubmed #17690930 No free full text.

Abstract: Cancer treatment-induced bone loss (CTIBL) is one of the most important side effects of adjuvant antineoplastic treatment in hormone-dependent neoplasms. Chemotherapy, GnRH analogs and tamoxifen can induce marked bone loss in premenopausal women with early breast cancer. Aromatase inhibitors (AIs) are replacing tamoxifen as the preferred treatment for postmenopausal women. As a class effect, steroidal (exemestane) and non-steroidal (anastrozole and letrozole) AIs increase bone turnover and cause bone loss (4%-5% over 2 years). When compared to tamoxifen, the risk of getting a clinical fracture under AI treatment is increased by 35%-50%. In patients with prostate cancer, androgen deprivation therapy (ADT) increases bone turnover, reduces bone mass (4%-5% per year) and increases the fracture rate depending on the duration of therapy. Zoledronic acid can prevent accelerated bone loss induced by goserelin in premenopausal women, by letrozole in postmenopausal women and by ADT in men. More limited data indicate that weekly alendronate or risedronate could also be effective for preventing CTIBL. Initiation of therapy early, prior to the occurrence of severe osteoporosis, rather than after, may be more effective. Bisphosphonate treatment should be considered in osteoporotic but also in osteopenic patients if other risk factor(s) for fractures are present.

Boonen S. · Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium. · Curr Opin Rheumatol. · Pubmed #16735842 No free full text.

Abstract: Patients with osteoporosis need a safe and effective treatment that reduces the risk of vertebral and non-vertebral fractures, leading to clinical benefits such as reduced back pain and height loss. Strontium ranelate corrects bone turnover, producing a more physiological state. Double-blind, placebo-controlled studies in postmenopausal osteoporosis show it to be effective in reducing vertebral and non-vertebral fracture risks. Treatment efficacy has been documented across a wide range of patient profiles, and appears to be independent of all the major determinants of fracture risk, including the severity of the disease at baseline, the number of prevalent fractures, and the age of the patient. This antifracture efficacy translates into clinical benefits, such as a 20% reduction in the rate of height loss and a 29% increase in the number of patients free of back pain. The effect of treatment with strontium ranelate on well-being has been assessed using the Quality-of-Life Questionnaire in Osteoporosis, which is a supplement to the 36-question Short-Form Health Survey. Treatment with strontium ranelate had a significant beneficial effect on the emotional, physical, and global Quality-of-Life Questionnaire in Osteoporosis scores compared with placebo. The rates of compliance with treatment were over 80% in phase III studies, reflecting the tolerability and safety profile and the ease of administration of this agent. Together with the antifracture data, the clinical benefits and quality of life data endorse the treatment of postmenopausal osteoporosis with strontium ranelate.

Boonen S, Vanderschueren D, Haentjens P, Lips P. · Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Belgium. · J Intern Med. · Pubmed #16704554 No free full text.

Abstract: Combined calcium and vitamin D supplementation is an essential component of the management of osteoporosis, supported by a strong scientific rationale. The types of individuals who should receive calcium and vitamin D supplements are those: (i) patients with documented osteoporosis receiving antiresorptive or anabolic treatment; (ii) patients receiving glucocorticoids; and (iii) individuals with or at high risk of calcium and/or vitamin D insufficiencies, in particular older women and men. This article describes the evidence base that supports targeting these groups. Benefits are most apparent when 800 IU day(-1) vitamin D is complemented with a dose of 1000-1200 mg day(-1) elemental calcium. Compliance is also key to optimizing clinical efficacy.

Boonen S, Bischoff-Ferrari HA, Cooper C, Lips P, Ljunggren O, Meunier PJ, Reginster JY. · Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium. · Calcif Tissue Int. · Pubmed #16622587 No free full text.

Abstract: Osteoporotic fractures are an extremely common and serious health problem in the elderly. This article presents the rationale for calcium and vitamin D supplementation in the prevention and treatment of osteoporotic fractures and reviews the literature evidence on the efficacy of this strategy. Two musculoskeletal risk factors are implicated in osteoporotic fractures in the elderly: the loss of bone mass due to secondary hyperparathyroidism and the increased propensity to falls. Calcium and vitamin D reverse secondary hyperparathyroidism with resultant beneficial effects on bone mineral density (BMD). Additionally, calcium and vitamin D supplementation significantly improves body sway and lower extremity strength, reducing the risk of falls. The effects of combined calcium and vitamin D on parathyroid function and BMD provide a strong rationale for the use of this therapy in the prevention and treatment of osteoporosis and osteoporotic fractures. There is general agreement that, in patients with documented osteoporosis, calcium and vitamin D supplementation should be an integral component of the management strategy, along with antiresorptive or anabolic treatment. Frail elderly individuals constitute another major target population for calcium and vitamin D because evidence from randomized studies in institutionalized elderly subjects demonstrates that these supplements reduce osteoporotic fracture risk, particularly in the presence of dietary deficiencies. However, the results of trials in community-dwelling subjects have been equivocal. Within the primary-care setting, further research is required to establish appropriate target subgroups for calcium and vitamin D supplementation; overall, the data are consistent with a benefit individuals with insufficient calcium and/or vitamin D, although patients with documented osteoporosis will derive further benefit in terms of fracture prevention from the addition of an antiresorptive agent.

Gaugris S, Heaney RP, Boonen S, Kurth H, Bentkover JD, Sen SS. · Rutgers University, Piscataway, NJ, USA. · QJM. · Pubmed #16006498 links to  free full text

Abstract: BACKGROUND: Vitamin D inadequacy has been studied extensively, due to concerns about ageing populations, associations with osteoporosis and other disorders (including non-musculoskeletal), and high prevalence. AIM: To review recent reports on the prevalence of vitamin D inadequacy among post-menopausal women with and without osteoporosis and/or other musculoskeletal diseases. DESIGN: Systematic review. METHODS: We reviewed publications in the past 10 years reporting prevalence estimates for vitamin D inadequacy, reported as serum 25(OH)D values below various levels. Thirty published studies in the English language were identified, from January 1994 through April 2004. RESULTS: In osteoporotic populations, the prevalence of 25(OH) vitamin D concentration <12 ng/ml ranged from 12.5% to 76%, while prevalence rates reached 50% to 70% of patients with a history of fracture(s) using a cut-off of 15 ng/ml. In post-menopausal women, the prevalence of 25(OH) vitamin D concentrations <or=20 ng/ml ranged from 1.6% to 86% for community-living and institutionalized women, respectively. The most common factors associated with inadequate vitamin D levels included limited sun exposure, lack of dietary vitamin D intake, nursing home environment, wintertime, and increasing age (over 70 years). DISCUSSION: The prevalence of inadequate vitamin D levels appears to be high in post-menopausal women, especially in those with osteoporosis and history of fracture. Vitamin D supplementation in this group might offer scope for prevention of falls and fracture, especially in elderly and osteoporotic populations.

Boonen S, Laan RF, Barton IP, Watts NB. · Division of Geriatric Medicine, Center for Metabolic Bone Diseases, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium. · Osteoporos Int. · Pubmed #15986101 No free full text.

Abstract: Most osteoporosis treatments have proven efficacy in reducing the risk of vertebral fractures, whereas evidence is less straightforward for prevention of non-vertebral fractures. Conclusions as to the efficacy of a treatment should be based primarily on analyses of the intention to treat (ITT) population rather than on exploratory subgroup analyses; however, non-vertebral anti-fracture efficacy has been largely derived by post-hoc subgroup analyses. This review and meta-analysis was performed to assess non-vertebral anti-fracture efficacy of several osteoporosis therapies, including a more stringent assessment of the ITT populations. Data on non-vertebral anti-fracture efficacy, a defined endpoint of the ITT analyses and confirmed by radiographs, were obtained from randomized, placebo-controlled, phase III clinical trials of at least 3-year duration. Meta-analyses were performed for the two bisphosphonates, alendronate and risedronate. Relative risks (RR), 95% confidence intervals (CI) and statistical significance for active treatment compared with placebo were calculated. Eleven clinical trials met the criteria for review, three of which showed statistically significant ( P < or =0.05) non-vertebral anti-fracture efficacy in the ITT population: two trials with risedronate and one trial with strontium. A meta-analysis showed significant reductions in the relative risk of non-vertebral fracture for both alendronate (RR=0.86; 95% CI: 0.76-0.97, P =0.012) and risedronate (RR=0.81; 95% CI: 0.71-0.92, P =0.001). Risedronate and strontium ranelate were the only treatments to show non-vertebral anti-fracture efficacy in this robust assessment of anti-fracture efficacy of osteoporosis therapy using ITT populations in trials of 3 years or more in duration. Risedronate was the only agent shown to demonstrate efficacy in more than one trial. Meta-analysis showed that both alendronate and risedronate provide non-vertebral anti-fracture efficacy.

Lindberg MK, Vandenput L, Movèrare Skrtic S, Vanderschueren D, Boonen S, Bouillon R, Ohlsson C. · Division of Endocrinology, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. · Minerva Endocrinol. · Pubmed #15877010 links to  free full text

Abstract: Loss of estrogens or androgens causes bone loss by increasing the rate of bone remodeling, and also causes an imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, treatment with androgens, as well as estrogens, maintains cancellous bone mass and integrity, regardless of age or sex. Both androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs) can exert these effects, but the relative contribution of these 2 pathways remains uncertain. Androgens, like estrogens, stimulate endochondral bone formation at the start of puberty, whereas they induce epiphyseal closure at the end of puberty, thus, they have a biphasic effect. Androgen action on the growth plate is, however, clearly mediated via aromatization into estrogens and interaction with ER alpha. Androgens increase, while estrogens decrease radial growth. This differential effect of the sex steroids may be important because bone strength in males seems to be determined by higher periosteal bone formation and, therefore, greater bone dimensions. Experiments in mice suggest that both the AR and ER alpha pathways are involved in androgen action on radial bone growth. ER beta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. This androgen action on bone is mediated by the AR and ER alpha.

Felsenberg D, Boonen S. · Department of Radiology and Nuclear Medicine, Centre of Muscle and Bone Research, Charité-Campus Benjamin Franklin, Free & Humboldt University, Berlin, Germany. · Clin Ther. · Pubmed #15763602 No free full text.

Abstract: BACKGROUND: Bone mineral density (BMD) measurements are the standard tool in the diagnosis of osteoporosis. However, recent developments in bone research show that a BMD measurement, while still important in a clinical setting, is in itself insufficient to accurately predict fracture risk or measure treatment effects of an antiosteoporosis drug. Clinical experience with patient follow-up strongly suggests that bone quality must also be taken into account. OBJECTIVES: The objectives of this paper are. (1) to describe the determinants of bone strength (structural and material properties of bone, both of which are affected by bone turnover) and their interrelationships, and (2) to provide a schematic explanation of these determinants of bone strength, which in this paper is referred to as the Bone Quality Framework. METHODS: Relevant information from the primary literature and review articles published in the English language were identified through a MEDLINE search of the medical literature, from 1990 to October 2004, in the fields of bone density, bone strength, bone quality, fracture risk, and fracture risk reduction. Additional publications were identified from the reference lists of the resulting articles. Identified publications relevant to the objectives of this review paper were selected. CONCLUSIONS: The Bone Quality Framework is presented in this paper as a means of summarizing and explaining the determinants of bone strength. In this framework, bone quality can be understood as an umbrella term that describes the set of characteristics that influence bone strength and explains the interrelationships of these characteristics. Bone strength depends on the structural and material properties of bone, both of which are influenced by the rate of bone turnover. Not all determinants of bone strength are well represented by a BMD measurement. The Bone Quality Framework presents an opportunity to examine all the determinants of bone strength. Greater understanding of the concept of bone quality will ultimately help improve the assessment of fracture risk and monitoring of patients receiving treatment for osteoporosis.

Boonen S, Vanderschueren D. · Leuven University Center for Metabolic Bone Diseases, Katholieke Universiteit Leuven, Leuven, Belgium. · Hosp Med. · Pubmed #15449490 No free full text.

This publication has no abstract.

Pfeifer M, Sinaki M, Geusens P, Boonen S, Preisinger E, Minne HW, Anonymous00282. · Institute of Clinical Osteology, Clinic DER FURSTENHOF, Bad Pyrmont, Germany. · J Bone Miner Res. · Pubmed #15231006 No free full text.

Abstract: Measures of musculoskeletal rehabilitation play an integral part in the management of patients with increased fracture risk because of osteoporosis or extraskeletal risk factors. This article delineates current scientific evidence concerning nonpharmacologic approaches that are used in conjunction with pharmacotherapy for prevention and management of osteoporosis. Fractures caused by osteoporotic fragility may be prevented with multidisciplinary intervention programs, including education, environmental modifications, aids, and implementation of individually tailored exercise programs, which are proved to reduce falls and fall-related injuries. In addition, strengthening of the paraspinal muscles may not only maintain BMD but also reduce the risk of vertebral fractures. Given the strong interaction between osteoporosis and falls, selection of patients for prevention of fracture should be based on bone-related factors and on risk factors for falls. Rehabilitation after vertebral fracture includes proprioceptive dynamic posture training, which decreases kyphotic posturing through recruitment of back extensors and thus reduces pain, improves mobility, and leads to a better quality of life. A newly developed orthosis increases back extensor strength and decreases body sway as a risk factor for falls and fall-related fractures. Hip fractures may be prevented by hip protectors, and exercise programs can improve strength and mobility in patients with hip fracture. So far, there is no conclusive evidence that coordinated multidisciplinary inpatient rehabilitation is more effective than conventional hospital care with no rehabilitation professionals involved for older patients with hip fracture. Further studies are needed to evaluate the effect of combined bone- and fall-directed strategies in patients with osteoporosis and an increased propensity to falls.

Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C. · Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium. · Endocr Rev. · Pubmed #15180950 links to  free full text

Abstract: Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs.Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth. ERbeta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males.In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. Such androgen action on bone is mediated by the AR and ERalpha.

Boonen S, Rizzoli R, Meunier PJ, Stone M, Nuki G, Syversen U, Lehtonen-Veromaa M, Lips P, Johnell O, Reginster JY. · Leuven University Centre for Metabolic Bone Diseases & Division of Geriatric Medicine, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium. · Osteoporos Int. · Pubmed #15069595 No free full text.

Abstract: A European Union (EU) directive on vitamins and minerals used as ingredients of food supplements with a nutritional or physiological effect (2002/46/EC) was introduced in 2003. Its implications for the use of oral supplements of calcium and vitamin D in the prevention and treatment of osteoporosis were discussed at a meeting organized with the help of the World Health Organization (WHO) Collaborating Center for Public Health Aspects of Rheumatic Diseases (Liège, Belgium) and the support of the WHO Collaborating Center for Osteoporosis Prevention (Geneva, Switzerland). The following issues were addressed: Is osteoporosis a physiological or a medical condition? What is the evidence for the efficacy of calcium and vitamin D in the management of postmenopausal osteoporosis? What are the risks of self-management by patients in osteoporosis? From their discussions, the panel concluded that: (1) osteoporosis is a disease that requires continuing medical attention to ensure optimal therapeutic benefits; (2) when given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active (particularly in patients with dietary deficiencies), safe, and effective for the prevention and treatment of osteoporotic fractures; (3) calcium and vitamin D are an essential, but not sufficient, component of an integrated management strategy for the prevention and treatment of osteoporosis in patients with dietary insufficiencies, although maximal benefit in terms of fracture prevention requires the addition of antiresorptive therapy; (4) calcium and vitamin D are a cost-effective medication in the prevention and treatment of osteoporosis; (5) it is apparent that awareness of the efficacy of calcium and vitamin D in osteoporosis is still low and further work needs to be done to increase awareness among physicians, patients, and women at risk; and (6) in order that calcium and vitamin D continues to be manufactured to Good Manufacturing Practice standards and physicians and other health care professionals continue to provide guidance for the optimal use of these agents, they should continue to be classified as medicinal products.

Boonen S, Haentjens P, Vandenput L, Vanderschueren D. · Center for Metabolic Bone Diseases Department of Geriatric Medicine, Katholieke Universiteit Leuven, Leuven, Belgium. · J Intern Med. · Pubmed #14687233 No free full text.

Abstract: Prospective studies have demonstrated that low bone mass correlates well with increased risk of osteoporotic fractures at various skeletal sites. Trials have likewise confirmed that enhancing bone mass with antiresorptive therapy reduces fracture incidence in individuals at risk. However, correlation of bone mineral density (BMD) increases with therapeutic risk reduction has proved less consistent than correlation of BMD decreases with greater fracture risk in the untreated. Indeed, various analyses have indicated that - even during treatment with potent bisphosphonates like alendronate and risedronate - BMD changes from baseline account for <30% of the reduction in vertebral fractures in treated women. It is clearly, therefore, that factors other than BMD are involved in the reduction of fracture risk achieved by antiresorptive therapies. According to recent micro-computed tomography imaging and other studies, antiresorptive therapy can help rebuild the microarchitecture of bone as well as strengthen the materials that go into it. When treating individuals with osteoporosis, these microarchitectural changes contribute to the reduction of fracture risk achieved by antiresorptive therapies.

Geusens P, Milisen K, Dejaeger E, Boonen S. · Biomedical Research Institute, Limburgs Universitair Centrum, Diepenbeek, Belgium. · J Br Menopause Soc. · Pubmed #14670194 No free full text.

Abstract: Older people are a major risk group for falls. 35-40% of over-65s living at home fall at least once a year, and between a third and a half of these fall twice or more. The figure rises to 50% for the over-80s. Falls contribute to the occurrence of fractures. Of all the fractures linked to osteoporosis and falls, hip fractures are the most important in terms of early death, functional dependence, and costs of care. Many identifiable risk factors have been shown to contribute to hip fracture risk, including low bone density, previous fractures, clinical risk factors for falls, and low body weight. Interaction has been found between falls and osteoporosis in the occurrence of fractures. Prospective studies are needed to evaluate whether a combined bone- and fall-directed therapy can further decrease the risk for fractures in patients with low bone density and an increased fall risk.

Geusens PP, Boonen S. · Department of Rheumatology, University Hospital, Maastricht, The Netherlands. · Horm Res. · Pubmed #12435898 No free full text.

Abstract: Osteoporosis is the result of an imbalance between bone resorption and bone formation. Currently, mainly drugs that inhibit bone resorption are available for the treatment of osteoporosis. A new approach in the treatment of osteoporosis is the use of anabolic agents that increase bone turnover, both bone formation and resorption. Growth hormone (GH) and insulin-like growth factors (IGFs) are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. We will review the evidence of GH and IGF-I in the pathophysiology and treatment of osteoporosis.