M. L. Brandi

Risedronate Rapidly Reduces the Risk for Nonvertebral Fractures in Women with Postmenopausal Osteoporosis

Prevention of nonvertebral fractures, which account for a substantial proportion of osteoporotic fractures, is an important goal of osteoporosis treatment. Risedronate, a pyridinyl bisphosphonate, significantly reduces clinical vertebral fracture incidence within 6 months. To determine the effect of risedronate on osteoporosis-related nonvertebral fractures, data from four large, randomized, double-blind, placebo-controlled, Phase III studies were pooled and analyzed. The population analyzed consisted of postmenopausal women, with and without vertebral fractures, who had low bone mineral density (lumbar spine T-score <−2.5). Patients received placebo (N = 608) or risedronate 5 mg daily (N = 564) for 1 to 3 years. At baseline, 58% had at least one prevalent vertebral fracture, and the mean lumbar spine T-score was −3.4. Among placebo-treated patients, the presence of prevalent vertebral fractures did not increase the risk of incident nonvertebral fractures overall, although fractures of the humerus and hip and pelvis were more common in patients who had prevalent vertebral fractures than in those who did not. Risedronate 5 mg significantly reduced the incidence of nonvertebral fractures within 6 months compared with control. After 1 year, nonvertebral fracture incidence was reduced by 74% compared with control (P = 0.001), and after 3 years, the incidence was reduced by 59% (P = 0.002). The results indicate that risedronate significantly reduces the incidence of osteoporosis-related nonvertebral fractures within 6 months.

Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.

Coordinator-based systems for secondary prevention in fragility fracture patients

The underlying causes of incident fractures—bone fragility and the tendency to fall—remain under-diagnosed and under-treated. This care gap in secondary prevention must be addressed to minimise both the debilitating consequences of subsequent fractures for patients and the associated economic burden to healthcare systems. Clinical systems aimed at ensuring appropriate management of patients following fracture have been developed around the world. A systematic review of the literature showed that 65% of systems reported include a dedicated coordinator who acts as the link between the orthopaedic team, the osteoporosis and falls services, the patient and the primary care physician. Coordinator-based systems facilitate bone mineral density testing, osteoporosis education and care in patients following a fragility fracture and have been shown to be cost-saving. Other success factors included a fracture registry and a database to monitor the care provided to the fracture patient. Implementation of such a system requires an audit of existing arrangements, creation of a network of healthcare professionals with clearly defined roles and the identification of a ‘medical champion’ to lead the project. A business case is needed to acquire the necessary funding. Incremental, achievable targets should be identified. Clinical pathways should be supported by evidence-based recommendations from national or regional guidelines. Endorsement of the proposed model within national healthcare policies and advocacy programmes can achieve alignment of the objectives of policy makers, professionals and patients. Successful transformation of care relies upon consensus amongst all participants in the multi-disciplinary team that cares for fragility fracture patients.

How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis

Oestrogen deficiency increases the rate of bone remodelling which, in association with a negative remodelling balance (resorption exceeding formation), results in impaired bone architecture, mass and strength. Current anti-osteoporotic drugs act on bone remodelling by inhibiting bone resorption or by promoting its formation. An alternative therapeutic approach is based on the concept of inducing opposite effects on bone resorption and formation. One therapeutic agent, strontium ranelate, was shown to induce opposite effects on bone resorption and formation in pre-clinical studies and to reduce fracture risk in postmenopausal osteoporotic patients. How strontium ranelate acts to improve bone strength in humans remains a matter of debate, however. This review of the most recent pre-clinical and clinical studies is a critical analysis of strontium ranelate’s action on bone resorption and formation and how it increases bone mass, microarchitecture and strength in postmenopausal osteoporotic women.

Natural and synthetic isoflavones in the prevention and treatment of chronic diseases

The evidence that natural isoflavones protect against several chronic diseases is both observational and experimental. In humans, epidemiologic findings clearly show a higher incidence of some common types of cancer (i.e., breast, prostate, and colon) and of coronary heart diseases in Western populations exposed to limited amounts of soybean isoflavones (i.e., genistein, daidzein) in the diet. Further evidence for cancer and cardiac protection and antiatherogenic effects resulting from soybean isoflavones administration has been noted in various experimental animal models. Isoflavones may also prevent postmenopausal bone loss and osteoporosis. In fact, genistein has been reported to be as active as estrogens in maintaining bone mass in ovariectornized rats. Moreover, the synthetic isoflavone derivative ipriflavone is able to reduce bone loss in various types of animal models of experimental osteoporosis providing a rationale on its use in the prevention and treatment of postmenopausal and senile osteoporosis in humans. The mechanism through which isoflavones may exert the abovementioned effects seems to depend, at least in part, on their mixed estrogen agonist-antagonist properties. An alternative hypothetical mechanism could derive from other biochemical actions of isoflavones such as inhibition of enzymatic activity, in particular protein kinases, or activation of an “orphan” receptor distinct from the estrogen type I receptor.

Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures

Vertebral compression fractures (VCFs) are the most prevalent fractures in osteoporotic patients. The classical conservative management of these fractures is through rest, pain medication, bracing and muscle relaxants. The aim of this paper is to review prospective controlled studies comparing the efficacy and safety of minimally invasive techniques for vertebral augmentation, vertebroplasty (VP) and balloon kyphoplasty (BKP), versus non-surgical management (NSM). The Fracture Working Group of the International Osteoporosis Foundation conducted a literature search and developed a review paper on VP and BKP. The results presented for the direct management of osteoporotic VCFs focused on clinical outcomes of these three different procedures, including reduction in pain, improvement of function and mobility, vertebral height restoration and decrease in spinal curvature (kyphosis). Overall, VP and BKP are generally safe procedures that provide quicker pain relief, mobility recovery and in some cases vertebral height restoration than conventional conservative medical treatment, at least in the short term. However, the long-term benefits and safety in terms of risk of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting. Referral physicians should be aware of VP/BKP and their potential to reduce the health impairment of patients with VCFs. However, VP and BKP are not substitutes for appropriate evaluation and treatment of osteoporosis to reduce the risk of future fractures.

What is the predictive value of MRI for the occurrence of knee replacement surgery in knee osteoarthritis

Knee osteoarthritis is associated with structural changes in the joint. Despite its many drawbacks, radiography is the current standard for evaluating joint structure in trials of potential disease-modifying osteoarthritis drugs. MRI is a non-invasive alternative that provides comprehensive imaging of the whole joint. Frequently used MRI measurements in knee osteoarthritis are cartilage volume and thickness; others include synovitis, synovial fluid effusions, bone marrow lesions (BML) and meniscal damage. Joint replacement is considered a clinically relevant outcome in knee osteoarthritis; however, its utility in clinical trials is limited. An alternative is virtual knee replacement on the basis of symptoms and structural damage. MRI may prove to be a good alternative to radiography in definitions of knee replacement. One of the MRI parameters that predicts knee replacement is medial compartment cartilage volume/thickness, which correlates with radiographic joint space width, is sensitive to change, and predicts outcomes in a continuous manner. Other MRI parameters include BML and meniscal lesions. MRI appears to be a viable alternative to radiography for the evaluation of structural changes in knee osteoarthritis and prediction of joint replacement.

Treatment of osteoporosis in men

SUMMARY Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline) are discussed. INTRODUCTION Awareness of osteoporosis in men is improving, although it remains under-diagnosed and under-treated. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) workshop was convened to discuss osteoporosis in men and to provide a report by a panel of experts (the authors). METHODS A debate with an expert panel on preselected topics was conducted. RESULTS AND CONCLUSIONS Although additional fracture data are needed to endorse the clinical care of osteoporosis in men, consensus views were reached on diagnostic criteria and intervention thresholds. Empirical data in men display similarities with data acquired in women, despite pathophysiological differences, which may not be clinically relevant. Men should receive treatment at a similar 10-year fracture probability as in women. The design of mixed studies may reduce the lag between comparable treatments for osteoporosis in women becoming available in men.

Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity

SummaryCutaneous adverse reactions are reported for many treatments including antiosteoporotic agents. This position paper includes an algorithm for their recognition. With early recognition and proper management, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization, rehydration, and systemic corticosteroids, if necessary, the prognosis is good.IntroductionCutaneous adverse reactions are reported for many therapeutic agents and observed in between 0% and 8% of treated patients depending on the drug. The antiosteoporotic agents are reputed to be safe in terms of cutaneous effects; however, there have been a number of case reports of cutaneous adverse reactions, which merit consideration. This was the subject of a Working Group meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis in April 2009, to focus on the impact of cutaneous adverse reactions and drug-induced hypersensitivity in the management of postmenopausal osteoporosis. We prepared this position paper following these discussions, and include an algorithm for their recognition.MethodsWe reviewed cutaneous adverse reactions observed with antiosteoporotic agents, including information from case reports, regulatory documents, and pharmacovigilance.ResultsThe cutaneous adverse reactions range from benign reactions including exanthematous or maculopapular eruption (drug rash), photosensitivity, and urticaria to the severe and potentially life-threatening reactions, angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Review of available evidence shows that cutaneous adverse reactions occur with all commonly used antiosteoporotic agents. Notably, there are reports of SJS and TEN for bisphosphonates, and of DRESS and TEN for strontium ranelate. These severe reactions remain very rare (<1 in 10,000 cases).ConclusionWith early recognition and proper management, including immediate and permanent withdrawal of the culprit agent, accompanied by hospitalization and rehydration and systemic corticosteroids if necessary, the prognosis is good.

Intravenous administration of alendronate counteracts the in vivo effects of glucocorticoids on bone remodeling.

The purpose of the investigation was to test the use of alendronate in the therapy of children affected by chronic rheumatic diseases and symptomatic drug-induced osteoporosis. Two courses of alendronate were intravenously administered to four girls with vertebral fractures that were glucocorticoid induced. Improvement of back pain and bone mineral density increase evaluated by DXA and conventional spine X-rays were observed. Our study supports the ABD-induced improvement of the negative effects of long-term therapy on bone mineral density in children with chronic rheumatic diseases.