Julien Paccou

Osteoporosis and mortality

Osteoporosis is classified as a public health problem by healthcare authorities because it is associated with an increased risk of potentially serious fractures. Osteoporotic fractures are known to generate a heavy burden of morbidity and financial cost [1]. However, recent data indicate that some osteoporotic fractures are also associated with excess mortality. These data have led to public health measures such as the addition by the World Health Organization of fracture prevention to the list of public health priorities [2] and the update on hip fractures issued recently by the statistics department of the French ministry of health (DREES [3]). Hip fractures constitute the most severe complication of osteoporosis because they can induce permanent physical disability, loss of self-sufficiency, institutionalization and, above all, an increased risk of death. Interestingly, two recent publications support the hypothesis that optimal osteoporosis management may affect the risk of death. Here, we will review the main data linking osteoporotic fractures overall (as opposed to hip fractures only) and mortality.

Bone loss in patients with HIV infection

The prognosis of HIV infection has been considerably improved by the introduction of antiretroviral drugs. However, the longer survival times are associated with the emergence of new complications including decreased bone mineral density (BMD) values and/or bone insufficiency fractures. A meta-analysis of studies published between 1966 and 2005 showed bone absorptiometry results indicating osteoporosis in 15% of HIV patients and osteopenia in 52%. Longitudinal studies found no evidence that antiretroviral drug therapy contributed to the occurrence of bone loss. Available data indicate uncoupling with increases in bone resorption markers and decreases in bone formation markers. In addition to conventional risk factors for osteoporotic fractures, factors in HIV-infected patients may include malnutrition (wasting syndrome), hypogonadism, disorders in calcium and phosphate metabolism, and HIV infection per se. In patients with established bone insufficiency, bisphosphonate therapy should be considered. Alendronate in combination with vitamin D and calcium supplementation has been found effective in improving BMD values.

Severity of osteoporosis: what is the impact of co-morbidities?

The co-morbidity profile varies widely across postmenopausal women with osteoporosis, and comorbidities often adversely affect the management of osteoporosis. There is a need for detailed information on the co-morbidities that may affect the course of osteoporosis by increasing the risk of subsequent fractures or inducing multiple fractures. We consequently reviewed the literature on the most common co-morbidities in adults older than 50 years of age, with special attention to published meta-analyses. We found that osteoporosis severity was increased not only by conventional risk factors, but also by a number of conditions including inflammatory bowel and joint diseases with or without glucocorticoid therapy, breast cancer and prostate cancer treated with chemotherapy or hormone therapy, diabetes (chiefly type 1), and celiac disease. Studies suggest an adverse impact of moderate renal failure and depression, although their methodological weaknesses preclude definitive conclusions. In practice, these co-morbidities should be taken into account when evaluating the fracture risk and making treatment decisions.

Reduced levels of serum IGF-1 is related to the presence of osteoporotic fractures in male idiopathic osteoporosis

INTRODUCTIONnThe pathophysiology of male idiopathic osteoporosis (MIO) remains unknown. The aim of this study was to evaluate the involvement of IGF-1 in MIO, and to explore the relationships between bone mineral density and serum levels of IGF-1 and sex hormones.nnnMETHODSnInclusion criteria were osteoporosis (T-score<-2.5 SD) and/or an osteoporotic fracture. The osteoporotic patients were included after an exhaustive work-up to exclude the principal causes of secondary osteoporosis. Serum levels of IGF-1, estradiol, testosterone, SHBG, markers of bone turnover, and bone mineral density were compared between 79 MIO and 26 healthy subjects.nnnRESULTSnA significant reduction in serum IGF-1 was found in MIO patients (p=0.0189). This remained significant after adjustment for body mass index (BMI). A negative correlation was found between SHBG and serum IGF-1 (r=-0.231, p=0.048). SHBG levels were higher in osteoporotic patients (p=0.001). The Free Testosterone Index (FTI, total testosterone/SHBG) (p=0.002) was also lower in MIO patients. After adjustment for FTI and BMI, a significant association was observed between IGF-1 level and the presence of an osteoporotic fracture, indicating an independent effect of IGF-1 level on fracture risk. The odds ratio (OR) for fracture for each SD decrease in IGF1 level was 1.8 [CI: 1.09-2.96] (p=0.021).nnnCONCLUSIONnOur study indicates a decrease in serum IGF-1 levels in MIO. This could be either the cause or the consequence of a disturbance in sex hormone metabolism with increased SHBG serum levels.

Cystic fibrosis-related bone disease.

Purpose of review This review highlights recently published data on the pathophysiology, guidelines and treatment of cystic fibrosis (CF)-related bone disease. Recent findings The exact role of the cystic fibrosis transmembrane conductance regulator (CFTR), specifically the &Dgr;F508 allele, has been investigated in F508del-CFTR homozygous mice and the F508del-CFTR mutation may contribute to CF-related bone disease by slowing new bone formation. The European Cystic Fibrosis Society has issued guidelines for bone mineral density assessment, management of low-trauma fractures and bisphosphonate therapy. A systematic review based on meta-analyses reports that oral and intravenous bisphosphonates both improve bone mineral density in CF patients, but no data are available concerning the reduction of low-trauma fractures. Summary European Cystic Fibrosis Society guidelines may help physicians to improve the management of CF-related bone disease.

Severe osteoporosis: diagnosis and follow-up. Lessons for clinical practice

The management of osteoporosis has improved considerably, leading to the development of new goals. A major concern today is the management of patients with severe osteoporosis, in whom the need for pharmacotherapy is clear [1]. Epidemiological data have established that osteoporosis is associated with severe complications [2,3]. Furthermore, osteoporosis is now recognized as a complication of several chronic diseases, whose presence adversely affects the management of osteoporosis. The ODISSEE task force (Osteoporosis DIagnosis and Surveillance of SEvErity) was established to answer practical questions regarding the management of severe osteoporosis, based on evidence in the literature. Several groups conducted an exhaustive literature review, and advice was obtained from a panel of French rheumatologists. The ODISSEE scientific committee then developed the first consensus statement on the diagnosis, follow-up and management of severe osteoporosis. This statement was validated by a panel of 70 French rheumatologists at the first national ODISSEE meeting held on November 13-14, 2009.

Region specific Raman spectroscopy analysis of the femoral head reveals that trabecular bone is unlikely to contribute to non-traumatic osteonecrosis

Non-traumatic osteonecrosis (ON) of the femoral head is a common disease affecting a young population as the peak age of diagnosis is in the 40u2009s. The natural history of non-traumatic ON leads to a collapse of the femoral head requiring prosthetic replacement in a 60% of cases. Although trabecular bone involvement in the collapse is suspected, the underlying modifications induced at a molecular level have not been explored in humans. Here, we examine changes in the molecular composition and structure of bone as evaluated by Raman spectroscopy in human end-stage ON. Comparing samples from femoral heads harvested from 11 patients and 11 cadaveric controls, we show that the mineral and organic chemical composition of trabecular bone in ON is not modified apart from age-related differences. We also show that the molecular composition in the necrotic part of the femoral head is not different from the composition of the remaining ‘healthy’ trabecular bone of the femoral head. These findings support that quality of trabecular bone is not modified during ON despite extensive bone marrow necrosis and osteocyte death observed even in the ‘healthy’ zones on histological examination.

Stabilized severe osteoporosis: should the treatment be stopped?

Several medications have been proven to decrease the risk of postmenopausal osteoporotic fractures of the spine, hip, or peripheral skeleton. However, the optimal duration of treatment with these medications has not been determined. The efficacy data come chiefly from controlled trials conducted over 3 to 5 years in elderly women at high risk for fractures. Some of these trials were followed by open-label extension phases that showed sustained bone mineral density gains over 7 to 10 years. The data pointing to a sustained decrease in the fracture rate beyond 4-5 years of treatment vary across studies and drugs but are generally scant and open to criticism. The published evidence does not suggest a need for stopping osteoporosis medications after the first 4-5 years out of concern about bisphosphonate-induced osteonecrosis of the jaw or alendronate-induced atypical fractures. Given that pharmacotherapy targets patients with severe osteoporosis, continued treatment beyond the first 5 years is probably warranted in most cases.

Defining treatment failure in severe osteoporosis

The management of postmenopausal osteoporosis has benefited from the recent introduction of several new drug classes and is now well standardized. However, none of the available osteoporosis drugs completely abolishes the occurrence of fractures. Therefore, criteria are needed to determine when the occurrence of a fracture during treatment indicates failure to respond to the drug. Such criteria would improve patient management. A panel of national osteoporosis experts was convened to discuss data from a literature review on severe osteoporosis (Osteoporosis DIagnosis and Surveillance of SEvErity, ODISSEE). The experts reached a consensus that an inadequate response to treatment for postmenopausal osteoporosis is the occurrence, in a patient with severe osteoporosis, adequate calcium and vitamin D intakes, and good treatment adherence, of any of the following: incident major fracture within the first treatment year, more than one minor insufficiency fracture, or a bone mineral density decrease by at least the smallest significant amount (0.03 g/cm(2)) after 5 years or earlier in the event of a minor fracture.

Management of patients with incident fractures during osteoporosis treatment.

Official recommendations are available for detecting osteoporosis and initiating osteoporosis medications in postmenopausal women. However, there are no recommendations about the management of patients with incident fractures despite osteoporosis therapy. Second-line osteoporosis treatments have been evaluated only based on laboratory and absorptiometry criteria. Nevertheless, we will try to answer the following questions: (1) What criteria should be used to determine whether a fracture during osteoporosis treatment indicates treatment failure (low-energy fracture, fracture not due to an intercurrent health condition, fracture of the type targeted by the osteoporosis treatment, sufficient treatment duration at occurrence of the fracture, and good adherence to the treatment and to vitamin D supplementation)? (2) In patients with treatment failure or an inadequate clinical response, defined as a fracture despite adherence to osteoporosis therapy for at least 1 year, what are the best treatment strategies?