[Effect of drugs for osteoporosis on cardiovascular diseases and effect of cardio vascular drugs on osteoporosis]. / Effet des médicaments de l'ostéoporose sur les maladies cardiovasculaires et effet des médicaments à visée cardiovasculaire sur l'ostéoporose.

Osteoporosis and cardiovascular diseases are epidemiologically associated. Calcification phenomena of atherosclerotic plaque involve cytokines and growth factors also involved in bone remodeling. Drugs given for either of these two conditions could act on these mechanisms. Can osteoporosis drugs have an influence on the occurrence of cardiovascular events? Conversely, can the treatment of hypertension alter the course of osteoporosis? It is possible that administration of high doses of calcium (1g/day) in patients who already have important dietary intake can increase the risk of myocardial infarction. Epidemiological studies show links between low serum vitamin D levels and cardiovascular disease but interventional studies show that vitamin D administration in moderately deficient subjects vitamin D does not prevent the occurrence of cardiovascular events. Cohort studies show a beneficial effect of beta-blockers and thiazides administered to hypertensive patients: they reduce by 20% risk of fracture of the proximal femur. Should we focus on these anti-hypertensive treatments for our patients with osteoporosis?

Osteoporosis and ischemic cardiovascular disease.

Osteoporosis and cardiovascular disease were long viewed as independent of each other. However, numerous epidemiological studies, which are discussed in the first part of this review, have provided incontrovertible evidence of a link. Thus, the risk of coronary artery disease and stroke is higher in patients with a history of osteoporotic fracture or low bone mineral density than in non-osteoporotic patients. In the other direction, patients with cardiovascular disease are at higher risk for bone loss and osteoporotic fracture. The link between osteoporosis and cardiovascular disease is due in part to shared conventional risk factors such as estrogen deprivation in women, smoking, low physical activity, and diabetes. In addition, atheroma plaque calcification involves cytokines and growth factors that also play a role in bone turnover, including proinflammatory cytokines (IL-6 and TNFα), osteoprotegerin, sclerostin, matrix GLA protein, and FGF-23. Several recent studies have provided support for these pathophysiological hypotheses. Thus, elevation of osteoprotegerin, sclerostin, or FGF-23 levels may explain and predict the occurrence of both osteoporotic fractures and cardiovascular events. The association between osteoporosis and cardiovascular disease found in most epidemiological and pathophysiological studies suggests a need for evaluating potential benefits from routine bone absorptiometry and osteoporotic fracture detection in patients with cardiovascular disease and from exercise testing and arterial Doppler imaging in patients with osteoporosis.

Trabecular Bone Score: Where are we now?

The Trabecular Bone Score is a rather new index obtained at the lumbar spine at the same time as a real bone mineral density. It was developed to reflect bone microarchitecture. It was proposed to be easily used in everyday practice as a surrogate of bone strength. Our aim was to review 1. technical points such as correlations between Trabecular Bone Score and bone microarchitectural parameters, Trabecular Bone Score and bone strength, the effects of dual-energy X-ray absorptiometry image spatial resolution, age, macroarchitecture, body mass index, and osteoarthritis, on Trabecular Bone Score, and 2. evidences to use Trabecular Bone Score for separating individuals with fragility fractures from controls, predicting fragility fractures, and for longitudinally monitoring changes related to treatments. Correlations between Trabecular Bone Score and bone microarchitectural parameters vary widely across bone sites, microarchitectural parameters, and study designs. In vivo, the Trabecular Bone Score explains little of the variance in trabecular microarchitectural parameters. We emphasize that it is a texture parameter. The Trabecular Bone Score is reduced in patients with fragility fracture. Several retrospective and prospective studies have shown its discriminative ability regarding the fracture risk. When combining the areal Bone mineral Density and Trabecular Bone Score, the Trabecular Bone Score remains a predictor of fracture but not the areal Bone Mineral Density. However in prospective studies, the best predictor of fracture remains hip areal bone mineral density. Due to the lack of evidence, we recommend not to use Trabecular Bone Score for following patients treated by anti-osteoporotic drugs.

Usefulness of bone density measurement in fallers.

The objective of this systematic literature review is to discuss the latest French recommendation issued in 2012 that a fall within the past year should lead to bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA). This recommendation rests on four facts. First, osteoporosis and fall risk are the two leading risk factors for nonvertebral fractures in postmenopausal women. Second, BMD measurement using DXA supplies significant information on the fracture risk independently from the fall risk. Thus, when a fall occurs, the fracture risk increases as BMD decreases. Third, osteoporosis drugs have been proven effective in preventing fractures only in populations with osteoporosis defined based on BMD criteria. Finally, the prevalence of osteoporosis is high in patients who fall and increases in the presence of markers for frailty (e.g., recurrent falls, sarcopenia [low muscle mass and strength], limited mobility, and weight loss), which are risk factors for both osteoporosis and falls. Nevertheless, life expectancy should be taken into account when assessing the appropriateness of DXA in fallers, as osteoporosis treatments require at least 12months to decrease the fracture risk. Another relevant factor is the availability of DXA, which may be limited due to geographic factors, patient dependency, or severe cognitive impairments, for instance. Studies are needed to better determine how the fall risk and frailty should be incorporated into the fracture risk evaluation based on BMD and the FRAX® tool.

Male osteoporosis: diagnosis and fracture risk evaluation.

Male osteoporosis is challenging to diagnose and to treat. Underestimation of the risk of male osteoporosis, the combined presence of several interwoven causative factors in many patients, and uncertainty regarding the absorptiometry cutoffs associated with fractures are major obstacles to the diagnosis of male osteoporosis and to the identification of men at risk for fractures. The lifetime risk of osteoporotic fracture is estimated at 15% among men older than 50 years. One-third of proximal femoral fractures occur in men, and the associated mortality rate is 2- to 3-fold that in women. In men, nearly half the cases of osteoporosis are related to disease, medications, or risk factors. Although the criteria for diagnosing male osteoporosis are not agreed on, the definitions developed by the World Health Organization can be used provided the reference population is composed of young males. An absorptiometry T-score < or = -2.5 is useful for diagnosing osteoporosis but fails to adequately predict the fracture risk. The identification of men at high risk for fractures requires a combined evaluation of bone mineral density data, clinical risk factors, and risk factors for falls.

Devising global strategies for fracture-risk evaluation.

Fracture prevention is the goal of osteoporosis treatment. Bone mineral density (BMD) has been the main criterion for deciding whether to initiate treatment, which is usually recommended when the BMD is less than -2.5 SDs from the mean in young women. However, the need to base treatment decisions on the overall fracture risk, rather than on BMD values alone, is now increasingly recognized. Several factors predict the fracture risk independently from BMD. Combining these factors to BMD may improve patient selection for osteoporosis therapy. In addition to low BMD values, factors associated with a high fracture risk include advanced age, prior fractures in the patient or family, low body mass index, smoking, glucocorticoid therapy, unfavorable profile of bone turnover markers, and risk factors for falls. There is no consensus yet about the best strategy for using these risk factors to assist in treatment decisions. A collaborative center set up by the World Health Organization is evaluating pooled data from prospective studies in order to better define high-risk patient subsets that are likely to benefit from osteoporosis treatment to prevent fractures. The results will serve to develop clinical guidelines for identifying high-risk patients.

Study of serum factors potentially involved in the pathogenesis of heterotopic bone formation after severe brain injury.

OBJECTIVE: To look for serum factors detectable early after head injury and predictive of heterotopic bone formation. PATIENTS AND METHODS: In this prospective study of a homogeneous population of 31 men with severe brain injury, blood samples were obtained 3 months after the accident, and levels of serum factors influenced by bone metabolism were compared between patients with and without heterotopic bone formation. As extensive fractures can influence serum factors, the patients without heterotopic bone formation were divided into two groups based on whether they had major fractures. Radionuclide bone scanning was used to validate patient classification. RESULTS: The group with heterotopic bone formation had significantly higher serum alkaline phosphatase levels (P < 0.01) and significantly lower serum leptin levels (P < 0.01), as compared to the other two groups. Body mass index and serum creatinine were comparable in the three groups. CONCLUSION: Leptin may be associated with the development of heterotopic bone formation. The antiosteogenic effect of leptin mediated by hypothalamic neurons may be impaired by hypothalamic damage related to severe brain injury.

[François Calot's concepts about the treatment of osteoarticular tuberculosis]. / Le traitement de la tuberculose ostêo-articulaire selon les conceptions du docteur François Calot.

François Calot proposed to cure the articular tuberculosis by punctures of the tuberculosis abscess and by immobilisation of the joint. He succeeded in many cases which had not to undergo surgery and his method was recognized as the best one till the arrival of the antibiotic (streptomycine) in 1948 which allowed to carry out surgery in the tuberculosis of bones and joints.