The osteoporosis care gap in Canada

BACKGROUND: The presence of a fragility fracture is a major risk factor for osteoporosis, and should be an indicator for osteoporosis diagnosis and therapy. However, the extent to which patients who fracture are assessed and treated for osteoporosis is not clear. METHODS: We performed a review of the literature to identify the practice patterns in the diagnosis and treatment of osteoporosis in adults over the age of 40 who experience a fragility fracture in Canada. Searches were performed in MEDLINE (1966 to January 2, 2003) and CINAHL (1982 to February 1, 2003) databases. RESULTS: There is evidence of a care gap between the occurrence of a fragility fracture and the diagnosis and treatment of osteoporosis in Canada. The proportion of individuals with a fragility fracture who received an osteoporosis diagnostic test or physician diagnosis ranged from 1.7% to 50%. Therapies such as hormone replacement therapy, bisphosphonates or calcitonin were being prescribed to 5.2% to 37.5% of patients. Calcium and vitamin D supplement intake was variable, and ranged between 2.8% to 61.6% of patients. CONCLUSION: Many Canadians who experience fragility fracture are not receiving osteoporosis management for the prevention of future fractures

A Cross-Species Analysis of a Mouse Model of Breast Cancer-Specific Osteolysis and Human Bone Metastases Using Gene Expression Profiling

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer-related death in women in the United States. During the advanced stages of disease, many breast cancer patients suffer from bone metastasis. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. <it>In vivo </it>models that mimic the breast cancer-specific osteolytic bone microenvironment are limited. Previously, we developed a mouse model of tumor-bone interaction in which three mouse breast cancer cell lines were implanted onto the calvaria. Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface.</p> <p>Methods</p> <p>In this study, we identified and used a TB microenvironment-specific gene expression signature from this model to extend our understanding of the metastatic bone microenvironment in human disease and to predict potential therapeutic targets.</p> <p>Results</p> <p>We identified a TB signature consisting of 934 genes that were commonly (among our 3 cell lines) and specifically (as compared to tumor-alone area within the bone microenvironment) up- and down-regulated >2-fold at the TB interface in our mouse osteolytic model. By comparing the TB signature with gene expression profiles from human breast metastases and an <it>in vitro </it>osteoclast model, we demonstrate that our model mimics both the human breast cancer bone microenvironment and osteoclastogenesis. Furthermore, we observed enrichment in various signaling pathways specific to the TB interface; that is, TGF-β and myeloid self-renewal pathways were activated and the Wnt pathway was inactivated. Lastly, we used the TB-signature to predict cyclopenthiazide as a potential inhibitor of the TB interface.</p> <p>Conclusion</p> <p>Our mouse breast cancer model morphologically and genetically resembles the osteoclastic bone microenvironment observed in human disease. Characterization of the gene expression signature specific to the TB interface in our model revealed signaling mechanisms operative in human breast cancer metastases and predicted a therapeutic inhibitor of cancer-mediated osteolysis.</p

Evaluation of therapeutic efficacy in osteoporosis

Evaluation of the efficacy of osteoporosis treatments poses a major challenge for clinical investigators. This paper addresses the question of whether increases in bone mass induced by therapy for osteoporosis are sufficient to determine the efficacy of that therapy, or whether long-term fracture endpoint studies are required. Osteoporosis has been defined as a systematic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. This association between bone mass and fracture risk has been found to be stronger than other well-recognized risk factor associations, such as blood pressure and risk of stroke. Although fracture endpoint studies would provide confirmation of the benefit of osteoporosis therapy, such trials require that several thousand patients be studied for many years, making such studies impractical as a means for providing data for the approval of new therapies. Determination of increased bone mass may provide data that are just as useful in evaluating therapeutic efficacy. The use of bone mass as the primary efficacy endpoint for those therapies that are associated with normal bone quality is justified by the well-documented relationship between bone mass and fracture risk observed in several epidemiological studies

Alendronate in the prevention of osteoporosis: 7-year follow-up

In a 3-year study followed by a 2-year open-label extension, alendronate sodium (ALN) maintained or increased bone mineral density (BMD) in 445 recently postmenopausal women with a spine BMD T-score &gt; -2. In a second 2-year extension, 84 women previously treated with either 5 or 10 mg ALN daily during the first 3 years and 5 mg ALN during the first extension (group A) were randomized to either 5 mg ALN or placebo (PBO). Another group of 59 women (group B) received 20 mg ALN during the first 2 years, PBO during year 3, and were then followed up without treatment during years 4-7. In group A, continuous ALN treatment for 7 years increased spine and trochanter BMD by 2.7-4.1 and 3.3-4.2%, respectively, while femoral neck BMD was maintained. Patients initially receiving 10 mg ALN maintained total body BMD, whereas those treated with 5 mg ALN experienced a small but significant loss after 7 years. Among women who received ALN 5 mg during years 4-7, those who had been treated with ALN 10 m