Yves Boutsen

Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone.

The aim of this study was to compare the action of two regimens of intravenous (iv) pamidronate in the primary prevention of glucocorticoid‐induced osteoporosis (GC‐OP). The primary purpose of the study was to determine whether any differences in bone mineral density (BMD) appeared after 1 year. A secondary endpoint aimed at assessing the remodeling parameters in order to better understand the mechanisms of action of the various regimens. Thirty‐two patients, who required first‐time, long‐term glucocorticoid therapy at a daily dose of at least 10 mg of prednisolone, were studied. Simultaneously with the initiation of their glucocorticoid treatment, patients also were randomly allocated to receive a single iv infusion of 90 mg of pamidronate at the start (group A); a first infusion of 90 mg of pamidronate followed, subsequently, by an iv infusion of 30 mg pamidronate every 3 months (group B); and a daily 800‐mg elemental calcium supplement given as calcium carbonate (group C), which also was taken by patients in groups A and B. Patients were matched for starting glucocorticoid doses, sex, menopausal status, and hormonal replacement therapy. Lumbar spine and hip (total and subregions) BMDs were measured at the outset and repeated at 6‐month intervals by dual‐energy X‐ray absorptiometry (DXA; Hologic QDR‐2000). Bone turnover was assessed by measurement of total and bone‐specific serum alkaline phosphatase activity (B‐ALP), serum osteocalcin (OC), and serum C‐telopeptide cross‐links of type I collagen (CTX). After 1 year, the mean BMD changes for groups A, B, and C were, respectively, 1.7, 2.3, and −4.6% at the lumbar spine; 1.2, 1.2, and −3.1% at the femoral neck; 1.0, 2.6, and −2.2% for the total hip region. No difference was observed between pamidronate regimens but a highly significant difference was observed between both pamidronate regimens and the control group at the lumbar spine (p < 0.001), at the femoral neck (p < 0.01), and for the total hip (p < 0.05). A significant decrease of serum C‐telopeptide was observed, after 3 months, in groups A and B (p = 0.029), but a sustained decrease of bone resorption over time was observed only in group B. As far as BMD evolution over 1 year was concerned, iv pamidronate, given either as a single infusion or once every 3 months, effectively achieved primary prevention of GC‐OP.

Primary prevention of glucocorticoid-induced osteoporosis with intermittent intravenous pamidronate: a randomized trial.

Abstract. The aim of this study was to assess whether early intermittent I.V. administration of disodium pamidronate can effectively achieve primary prevention of glucocorticoid-induced osteoporosis (GIOP). A total of 27 in- or outpatients who required first-time, long-term corticosteroid therapy at a daily dose of at least 10 mg prednisolone were studied. Patients were randomly selected to receive either pamidronate and calcium or calcium alone. Patients allocated to pamidronate treatment (pamidronate group) received a first intravenous infusion of 90 mg pamidronate simultaneously with the initiation of their steroid treatment. Subsequently, they received 30 mg pamidronate, intravenously, every 3 months, for as long as steroid therapy was continued. As with the control patients (calcium group), they were put on a daily 800-mg elemental calcium supplement given as calcium carbonate. Lumbar spine and hip (total and subregions) bone mineral densities (BMDs) were measured at the start and every 3-months by dual-energy X-ray absorptiometry (Hologic® QDR-2000). Over 1 year, the pamidronate group showed a significant BMD increase in the lumbar spine (3.6%), and at all sites of the hip (2.2% at the femoral neck). In the calcium group, a significant BMD reduction was registered at the lumbar spine (−5.3%) and at the femoral neck (−5.3%). Differences between the groups were significant at all sites measured. Intermittent intravenous pamidronate effectively achieves primary prevention of GIOP, as assessed by BMD measurements over 1 year.

Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: a consensus document of the Belgian Bone Club

Objectives:  To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti‐resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency.

Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club

Several drugs are available for the management of postmenopausal osteoporosis. This may, in daily practice, confuse the clinician. This manuscript offers an evidence-based update of previous treatment guidelines, with a critical assessment of the currently available efficacy data on all new chemical entities which were granted a marketing authorization. Osteoporosis is widely recognized as a major public health concern. The availability of new therapeutic agents makes clinical decision-making in osteoporosis more complex. Nation-specific guidelines are needed to take into consideration the specificities of each and every health care environment. The present manuscript is the result of a National Consensus, based on a systematic review and a critical appraisal of the currently available literature. It offers an evidence-based update of previous treatment guidelines, with the aim of providing clinicians with an unbiased assessment of osteoporosis treatment effect.

Evidence-based guidelines for the treatment of postmenopausal osteoporosis: a consensus document of the Belgian Bone Club

Osteoporosis is widely recognized as a major public health concern. The cumulative lifetime fracture risk for a 50-year woman with osteoporosis is as high as 60% [1]. In Belgium, the annual costs of osteoporotic fractures are currently estimated in the range of 150 million euros, on a societal perspective [2]. Effective fracture prevention would have a major impact on women’s morbidity and to a lesser extend mortality. The availability of new therapeutic agents has made clinical decision-making in osteoporosis more complex [3]. Because individual clinicians cannot systematically collect all the evidence bearing on the efficacy of osteoporosis therapies, they require summaries for consistent therapeutic patterns [3]. As recommended by the International Osteoporosis Foundation (IOF), nation-specific guidelines are requested to take into consideration the specificities of each and every health care environment. The present document is the result of a national consensus, based on a systematic review and a critical appraisal of the currently available literature. It offers an evidence-based update to previous Belgian Bone Club treatment guidelines [4], with the aim of providing clinicians with an unbiased assessment of osteoporosis treatment effect.

Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club

This consensus article reviews the various aspects of the non-pharmacological management of osteoporosis, including the effects of nutriments, physical exercise, lifestyle, fall prevention, and hip protectors. Vertebroplasty is also briefly reviewed. Non-pharmacological management of osteoporosis is a broad concept. It must be viewed as an essential part of the prevention of fractures from childhood through adulthood and the old age. The topic also includes surgical procedures for the treatment of peripheral and vertebral fractures and the post-fracture rehabilitation. The present document is the result of a consensus, based on a systematic review and a critical appraisal of the literature. Diets deficient in calcium, proteins or vitamin D impair skeletal integrity. The effect of other nutriments is less clear, although an excessive consumption of sodium, caffeine, or fibres exerts negative effects on calcium balance. The deleterious effects of tobacco, excessive alcohol consumption and a low BMI are well accepted. Physical activity is of primary importance to reach optimal peak bone mass but, if numerous studies have shown the beneficial effects of various types of exercise on bone mass, fracture data as an endpoint are scanty. Fall prevention strategies are especially efficient in the community setting, but less evidence is available about their effectiveness in preventing fall-related injuries and fractures. The efficacy of hip protectors remains controversial. This is also true for vertebroplasty and kyphoplasty. Several randomized controlled studies had reported a short-term advantage of vertebroplasty over medical treatment for pain relief, but these findings have been questioned by recent sham-controlled randomized clinical studies.

Loading and Skeletal Development and Maintenance

Mechanical loading is a major regulator of bone mass and geometry. The osteocytes network is considered the main sensor of loads, through the shear stress generated by strain induced fluid flow in the lacuno-canalicular system. Intracellular transduction implies several kinases and phosphorylation of the estrogen receptor. Several extra-cellular mediators, among which NO and prostaglandins are transducing the signal to the effector cells. Disuse results in osteocytes apoptosis and rapid imbalanced bone resorption, leading to severe osteoporosis. Exercising during growth increases peak bone mass, and could be beneficial with regards to osteoporosis later in life, but the gain could be lost if training is abandoned. Exercise programs in adults and seniors have barely significant effects on bone mass and geometry at least at short term. There are few data on a possible additive effect of exercise and drugs in osteoporosis treatment, but disuse could decrease drugs action. Exercise programs proposed for bone health are tedious and compliance is usually low. The most practical advice for patients is to walk a minimum of 30 to 60 minutes per day. Other exercises like swimming or cycling have less effect on bone, but could reduce fracture risk indirectly by maintaining muscle mass and force.

Management of patients with Paget's disease: a consensus document of the Belgian Bone Club.

Paget’s disease of bone (PDB) is a potentially crippling condition. Pain, fracture, spinal stenosis, nerve entrapment, vascular steal syndrome, secondary osteoarthritis, bone deformity, dental problems, deafness, excessive bleeding during orthopaedic surgery, rare sarcomatous degeneration, and hypercalcaemia constitute complications that may impair the quality of life. The therapeutic approach varies from symptomatic (analgesics, anti-inflammatory drugs) to more specific drugs such as increasingly potent bisphosphonates. Studies such as the PRISM study should in the future help to determine the superiority or not of aggressive treatment over symptomatic treatment in the prevention of complications. Various oral and/or intravenous (I.V.) bisphosphonates have been tested and are currently on the market. The most recently available nitrogen-containing bisphosphonate, I.V. zoledronic acid, is the most potent therapy available for the treatment of PDB. Its therapeutic efficacy, its long-term effect on biologic activity and its good tolerance currently supports its use as a first-line therapeutic option in patients suffering from PDB.

Adult onset of multifocal eosinophilic granuloma of bone: a long-term follow-up with evaluation of various treatment options and spontaneous healing.

Abstract: We report a case of multifocal–monosystemic Langherhans cell histiocytosis (LCH), formerly usually referred to as eosinophilic granuloma (EG) of bone. The condition developed in a 36-year-old man. A notable infrequent thoracic spine location and two successive distinct costal lesions were observed. Both the first costal site and the vertebral location healed spontaneously; the second costal lesion underwent biopsy resection. The patient’s disease course with an 8-year follow-up is discussed with reference to various treatment options, emphasising in selected cases a watchful conservative approach, in view of the widely documented potential for spontaneous healing.

Is there a place for bone turnover markers in the assessment of osteoporosis and its treatment

As populations age, the number of osteoporotic fractures will increase. Bone mineral density (BMD) measurement remains the major way to diagnose osteoporosis and to indicate therapy. The FRAX tool, based on clinical risk factors, estimates the 10-year risk of hip and major osteoporotic fractures. The association of BMD and FRAX measurements has improved the identification of patients who are most at risk. However, some patients can still be overlooked and denied therapy. It is sound that adding the measure of bone turnover markers to the former risk factors and their follow-up during therapy could best address the efficacy of treatment of osteoporosis. Whether this behavior is cost-effective remains to be settled.