Mesenchymal stem/progenitor cells (MSCs) can differentiate into adipocytes, muscle cells, osteoblasts, or cartilage and possess potential for tissue repair in patients with osteoporosis, diseased joints, and myocardial infarction. Many groups have investigated strategies involving the infusion of MSCs for the purpose of regenerative therapy; however, problems concerning MSC homing to diseased sites and the use of allogeneic MSCs have limited this approach. Therefore, the ability to use pharmacological agents to induce the differentiation of resident MSCs toward a certain lineage in vivo is an important therapeutic goal. In a recent study [1], the authors report that bortezomib, a clinically available proteasome inhibitor active against myeloma, induces the differentiation of MSCs into osteoblasts, resulting in new bone formation.

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Bone remodeling is a complex process that is regulated by an interplay between circulating hormones and locally produced factors that act in a concerted manner to regulate osteoblast and osteoclast activity. There has been recently increasing interest in the role that the nervous system and neurotransmitters play in the regulation of bone remodeling. Reflecting this fact, the endocannabinoid pathway has recently been implicated as are important regulator of bone turnover and bone mass. The type 2 cannabinoid receptor (CB2) has been reported to regulate bone mass, but conflicting results have been reported with regard to its effects on bone resorption and osteoclast function. In this study [1], the authors investigated the role that CB2 plays in regulating bone mass and osteoclast function using a combination of pharmacological and genetic approaches.

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Previous studies have shown increased bone density and reduced risk of fracture in patients taking thiazide diuretics. In vitro, a direct effect of thiazides on osteoblasts has been reported. However, the long-term effects of low-dose thiazides on mineral metabolism have not been reported in normal subjects. The authors of this study [1] conducted a randomized, double-blinded trial in normal subjects aged 60 to 79 years, using hydrochlorothiazide 12.5 or 25 mg/d or placebo for 3 years. Subjects were encouraged to maintain calcium intake of 1 to 1.5 g/day. Measurements of serum and urine calcium metabolism were done at baseline, 6 months, and yearly. Data were analyzed in 88 men and 177 women who had taken study medication. Adjusted changes in the measurements from baseline to 1 and 3 years were compared among groups.

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The fracture risk assessment tool (FRAX®) tool has recently become available to compute the 10-year probability of fractures in men and women from clinical risk factors (CRFs) with or without the measurement of femoral neck bone mineral density (BMD). The aim of this study [1] was to develop a case-finding strategy for men and women from the UK at high risk of osteoporotic fracture by delineating the fracture probabilities at which BMD testing or intervention should be recommended. Fracture probabilities were computed using the FRAX® tool calibrated to the epidemiology of fracture and death in the UK. An intervention threshold was set by age in men and women, based on the fracture probability equivalent to that of women with a history of a prior osteoporosis-related fracture. In addition, assessment thresholds for the use of BMD testing were explored. Assessment thresholds for the measurement of BMD followed current practice guidelines where individuals were considered to be eligible for assessment in the presence of one or more CRF. An upper assessment threshold (ie, a fracture probability above which patients could be treated without recourse to BMD), was based on optimization of the positive predictive value of the assessment tool. The consequences of assessment and intervention thresholds on the requirement for BMD test and interventions were assessed using the distribution of clinical risk factors and femoral neck BMD for women in the source cohorts used for the development of the FRAX® models.

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