[Innovations in physical and rehabilitation medicine]. / Innovations en médecine physique et réadaptation.

Over the last decade, Physical and Rehabilitation Medicine (PRM) is a medical specialty that has evolved considerably in the various fields that concern it : from the management of low back pain and lumbosciatalgia or osteoporosis in a multidisciplinary manner, through the use of new technologies in neuro-locomotor rehabilitation and robotisation in amputee patients for example, the development of regenerative medicine and prevention in sports traumatology and, finally, the progress of electrophysiology techniques for the diagnosis of small-fibre neuropathies. These various advances will be discussed in this article.

Au cours de la dernière décennie, la Médecine Physique et Réadaptation (MPR) est une spécialité médicale qui a fortement évolué dans les différents domaines qui la concernent : de la prise en charge des lombalgies et lombosciatalgies ou encore de l'ostéoporose de manière pluridisciplinaire, en passant par l'utilisation des nouvelles technologies en rééducation neuro-locomotrice et de la robotisation en rééducation, chez les patients amputés par exemple, le développement de la médecine à vocation régénérative et la prévention en traumatologie du sport et, enfin, les progrès des techniques d'électrophysiologie pour le diagnostic des neuropathies à petites fibres. Ces différentes avancées seront abordées dans cet article.

[OSTEOPOROSIS AND PERSONALIZED MEDICINE]. / OSTÉOPOROSE ET MÉDECINE PERSONNALISÉE.

Osteoporosis is at the very early stages of the implementation of personalized medicine. However, the development of FRAX®, an algorithm offering the opportunity to calculate, in an individual patient, his/her 10-year fracture risk improves the decision process on the appropriateness to initiate a pharmacological treatment. This algorithm helps the physician to select drugs which are active on non-vertebral fractures only in high risk patients. Taking into consideration patients' preferences, when selecting a therapeutic option, will improve long term adherence and subsequently efficacy and efficiency of the treatments. Attempts to define the natural course of osteoporosis or the response to therapy in individual patients by assessing their genetic profile remains, so far, inconclusive.

[Treatment of post-menopausic osteoporosis: what's new in 2014?]. / Traitement de l'ostéoporose post-ménopausique: quoi de neuf en 2014?

Management of osteoporosis involves both non pharmacological approaches, including changes in lifestyle and dietary habits combined, in patients at high risk of fracture or presenting with an established osteoporosis, to the use of drugs. Besides supplementation in calcium and vitamin D (at daily doses of 1 gr and 800 IU) in patients whose dietary intakes do not cover the recommended daily allowances, medications to be used for the management of osteoporosis may include inhibitors of bone resorption (bisphosphonates, denosumab and selective estrogen receptor modulators), stimulators of bone formation (teriparatide) or chemical entities decreasing bone resorption and stimulating bone formation (strontium ranelate). The selection of a particular medication, for a single individual patient, will depend on the severity of the disease as well as on the patient's believes and expectations. Local, skeletal and systemic tolerance of the various drugs should also be taken into account.

Relationship between whole plasma calcitonin levels, calcitonin secretory capacity, and plasma levels of estrone in healthy women and postmenopausal osteoporotics.

The exact role of calcitonin (CT) in the pathogenesis of postmenopausal osteoporosis remains unknown. Whole plasma calcitonin (iCT) basal levels, metabolic clearance rate (MCR), and production rate (PR) of CT were measured in 9 premenopausal and 16 postmenopausal women, including 11 osteoporotics (OP). Basal iCT levels were statistically lower in postmenopausal women than in the premenopausal group (P less than 0.01) and strongly correlated (r = 0.72; P less than 0.001) with estrone circulating levels (E1). MCR were similar in all groups. PR were similar in eugonadal women between 22 (mean +/- SD = 30.9 +/- 9.9 micrograms/d) and 37 yr (mean +/- SD = 25.5 +/- 11.1 micrograms/d) premenopausal women. In healthy postmenopausal women PR were reduced, but not significantly (mean +/- SD = 19.5 +/- 6.95 micrograms/d), whereas osteoporotic patients presented a highly significant reduction of CT PR (mean +/- SD = 9.8 +/- 4 micrograms/d) (P less than 0.01). Because there is a strong relationship between E1 and PR (r = 0.64; P less than 0.001), CT secretory capacity appears to be modulated by estrogen circulating levels. This modulation leads to a menopause-related decrease in iCT. In osteoporotics, an independent impairment of CT production drastically lowers PR and basal iCT levels. CT might be one of the determining factors in the pathogenesis of postmenopausal osteoporosis.

[Value of bone densitometry for the diagnosis and monitoring of osteoporotic patients: integration with biological and clinical risk factors]. / Intérêt de la densitométrie osseuse dans le dépistage et le suivi thérapeu- tique des patients ostéoporotiques: intégration avec les facteurs cliniques et biologiques.

The diagnosis of osteoporosis and the monitoring of antiosteoporosis therapies imply a better and more rational use of bone densitometry. The optimal prescription modalities of this fundamental examination are favorably correlated with the efficacy of modern therapeutics. The rationale of this article is to provide the general practitioner with a factual update on the diagnostic and prognostic use of bone densitometry.

Long-term (3 years) prevention of trabecular postmenopausal bone loss with low-dose intermittent nasal salmon calcitonin.

The long-term effect of intermittent low-dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow-up to a previously published study. Randomized controlled group comparison was made of 287 healthy women with 6-36 months of natural menopause and no treatment interfering with calcium metabolism at an outpatient clinic for research in bone and cartilage metabolism. The 287 women were randomly allocated to 3 years of treatment with either 500 mg/day, 5 days/week of calcium or the same amount of calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of 186 women complied with the study protocol throughout. The main outcome measures were bone mineral density of the lumbar spine (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in bone mineral density after 36 months showed a positive (p < 0.05) outcome (1.8 +/- 5.7%; mean +/- SD) in the group treated with salmon calcitonin and calcium and a significant (p < 0.01) loss (-5.8 +/- 4.8%) in patients receiving calcium alone. The difference between the evolution of the two groups was significantly (p < 0.01) different after 6 months of treatment and remained so until the end of the study. No significant changes were recorded in biochemical parameters reflecting bone turnover. As previously shown during a 1 year follow-up, nasal salmon calcitonin given at low dose and intermittently, in association with calcium, can counteract trabecular postmenopausal bone loss.

Efficacy and safety of drugs for Paget's disease of bone.

Paget's disease of bone is characterized by an anarchic bone turnover starting with excessive resorption caused by structural and functional abnormalities involving osteoclasts. Calcitonin and bisphosphonates are now considered as the main therapeutic approaches for this disease. Daily parenteral administration of calcitonin to patients with Paget's disease of bone results in a significant fall in serum alkaline phosphatase and urinary hydroxyproline levels. This treatment has also been reported to be effective in relieving clinical symptoms of the disease, mainly bone pain. The drawbacks of injectable calcitonin have stimulated interest in alternative routes of delivery. Substantial evidence of calcitonin bioavailability and bioefficacy equivalent to those of parenteral administration is currently available for only two alternative routes: nasal spray and rectal suppository. Since many results have been published showing a dramatic effect of several bisphosphonates in Paget's disease of bone, nasal and rectal calcitonin are no longer considered as the treatments of choice in this condition. A major advantage of the use of bisphosphonates over calcitonin in Paget's disease is that biochemical and histologic suppression of disease activity may persist for many years after the cessation of treatment. Oral etidronate and intravenous pamidronate have been extensively used and have provided satisfactory benefits to the patient. Since the risk/benefit ratio of alendronate does not appear to be completely positive, it is likely that the future of treatment of Paget's disease of bone will be based on the oral formulation of the new bisphosphonates, including tiludronate, risedronate or dimethyl-pamidronate.

Biological and clinical assessment of a new bisphosphonate, (chloro-4 phenyl) thiomethylene bisphosphonate, in the treatment of Paget's disease of bone.

Several Biophosphonates have been used as therapeutic agents for Paget's bone disease. (Chloro-4 phenyl)thiomethylene-bisphosphonate (CIPsMBP) has recently been shown to have significant antiosteoclastic activity while an affect of CIPsMBP on mineralization was only observed at high doses. We tested this drug for 6 months in 23 pagetic patients distributed in three groups. Gr 1 (n = 5) receiving 200 mg/day showed a decrease of serum alkaline phosphatase (SAP) to 42 +/- 4% (p less than 0.01) of initial value (100%) while hydroxyprolinuria/creatinuria ratio (OH/Cr) dropped to 69 +/- 8% of baseline. In 4 patients receiving 400 mg/day, SAP improved to 48 +/- 9% of initial value (p less than 0.01) and OH/Cr to 40 +/- 3% (p less than 0.01). In the last group (n = 14) receiving 200 mg/day for 3 months, and 400 mg/day thereafter up to the 6th month SAP decreased to 53 +/- 4% and OH/Cr to 62 +/- 6% of initial value (p less than 0.01). Clinical improvement was significant from the first month of treatment. No resistance (mean decrease of SAP lower than 30%) was recorded and no radiological or clinical evidence of mineralization defect appeared. The clinical and biological tolerance was excellent throughout the study.

A double-blind, placebo-controlled, dose-finding trial of intermittent nasal salmon calcitonin for prevention of postmenopausal lumbar spine bone loss.

PURPOSE: Nasal administration of salmon calcitonin (SCT) has been suggested for preventing trabecular bone loss during the first years following the menopause, but no conclusive evidence has appeared about the minimal effective dose. Since nasal calcitonin is highly expensive, it makes sense to define this dose. PATIENTS AND METHODS: We performed a double-blind, placebo-controlled, randomized, single-center study with a 3-arm parallel-group design. The subjects were 251 healthy women who had experienced natural menopause within the past 6 to 72 months and were not affected by any diseases or treatments that interfere with calcium metabolism. They were randomly allocated in groups of 6 to receive intranasal SCT 50 IU (n = 84), SCT 200 IU (n = 84), or placebo (n = 83). All treatments were given on 5 consecutive days per week. Statistical analysis was based on two populations: intention-to-treat (IT) and valid completers (VC). The main assessments performed were bone mineral density of the lumbar spine (LSBMD) and biochemical parameters reflecting bone turnover (serum alkaline phosphatase, urinary calcium/creatinine, and hydroxyproline/creatinine ratios). RESULTS: Changes over the treatment period were comparable in the IT and VC populations. In the group receiving the placebo, LSBMD decreased from baseline to end point by a mean of 6.28% (95% confidence interval [CI] -7.69 to -4.89) in the IT population and 6.98% (95% CI -8.86 to -5.11) in the VC population (P = 0.0001, end LSBMD versus baseline LSBMD). LSBMD increased slightly with the 50-IU/d dose of SCT, by 0.82% (95% CI -0.26 to 1.89) in the IT population, and 0.51% (95% CI -0.69 to 1.72) in the VC (P = NS, versus baseline). Subjects who received SCT 200 IU/d experienced significant increases of 2.03% (95% CI 0.92 to 3.15) in the IT population and 2.26% (95% CI 1.01 to 3.51) in the VC (both P = 0.001). The difference between the evolution of the combined groups receiving nasal SCT and the group treated with the placebo was highly significant (P = 0.0001). No significant changes were recorded in biochemical parameters reflecting bone turnover. CONCLUSIONS: SCT 50 IU/d administered nasally and intermittently appears to prevent lumbar bone loss in nonobese early postmenopausal women.

Calcitonin and postmenopausal bone loss.

In order to establish the role of calcitonin (CT) in postmenopausal bone loss, we studied CT metabolism in 25 pre- and postmenopausal women. Postmenopausal women presented a highly significant reduction of CT basal levels compared to premenopausal females (p less than 0.01). Also, production rates of CT in osteoporotics were significantly lower than in either young premenopausal (18-25 years old), older premenopausal (35-40 years old), or postmenopausal healthy subjects. In a study in rabbits, we found that injection of CT, along with equimolar amounts of anti-SCT antibodies extracted from serum of pagetic patients, did not inhibit the hypocalcemic response to the hormone, thus demonstrating that resistance to CT treatment cannot be accounted for by antibody production. In a subsequent clinical study in patients with Paget's disease of bone, we found that 200 IU/day of salmon CT (SCT), given by nasal spray, improved both clinically and biochemically the activity of the disease, as demonstrated by 37 +/- 4% decrease of serum alkaline phosphatase and 35 +/- 5% fall of urinary excretion of hydroxyproline after six months of therapy. The effectiveness of CT as nasal spray was further tested in healthy women at an early stage of menopause. A 12-month course of intranasal SCT counteracted early postmenopausal bone loss, presumably by inhibiting bone resorption. In conclusion, intranasal CT seems to be a very attractive alternative to be considered for the prevention of postmenopausal osteoporosis.

Thromboxane and prostacyclin release in adult respiratory distress syndrome.

Plasma thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured in 84 patients at risk of developing adult respiratory distress syndrome (ARDS) (44 patients following multiple trauma, 29 patients following abdominal surgery and 11 patients with acute pancreatitis). Forty-nine of these 84 patients developed an ARDS. High (greater than 140 pg/ml plasma) TXB2 values were found in 52/84 patients. The median values of TXB2 were: 360 pg/ml in multiple injured, 250 pg/ml in abdominal surgery and 410 pg/ml in acute pancreatitis patients. The median TXB2 value was 575 pg/ml in patients developing ARDS and 140 pg/ml in those without this complication: this difference was statistically significant (p less than 0.05). The median values of 6-keto-PGF1 alpha were 55 pg/ml in multiple injured, 25 pg/ml in abdominal surgery and 120 pg/ml in acute pancreatitis patients. The median 6-keto-PGF1 alpha value was 122 pg/ml in ARDS patients and 25 pg/ml in non-ARDS patients (statistically significant: p less than 0.05). High TXB2 and 6-keto-PGF1 alpha values were particularly related to sepsis in abdominal surgery patients (p less than 0.05) and in multiple injured patients (p less than 0.01). No relation could be established between abnormal TXB2 or 6-keto-PGF1 alpha values and death. High TXB2 values often persisted for several days and were observed particularly at the time ARDS diagnostic criteria were fulfilled.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prevention of hip fractures in the elderly: where are we in 2003?]. / Prévention de la fracture de la hanche chez le sujet âgé: où en sommes-nous en 2003?

Osteoporosis in very elderly subjects is now considered, in most developed and several developing countries as a major social, clinical and financial burden. While many compounds have been investigated in the prevention or treatment of spinal fractures, few of them have unequivocally demonstrated their ability to reduce the risk of non vertebral and more specifically hip fractures in the very elderly. This situation may seem highly paradoxical since hip fractures are unanimously considered to be the most dramatic and disabling consequence of osteoporosis. The present article reviews the current evidence available to justify anti-osteoporotic medications to be recommended to very elderly subjects, in the perspective of reducing their risk of appendicular fractures.

[Indications for epidural steroids in back pain and in radiculopathy]. / Indications des corticoïdes par voie péridurale dans les douleurs rachidiennes et radiculaires.

Back pain is very frequent in western countries and it represents a very high social cost. The treatment is based on five modalities: medication, physiotherapy, invasive technics, rehabilitation programs and psycho-social approaches. Several treatments may be proposed simultaneously and introduced gradually. Steroid administration by epidural injection is frequently used in Belgium, even though no prospective randomised studies have shown a real benefit over the long term. The indications for epidural injection must be carefully chosen. These include subacute pain (less than six months) in the lower limbs despite a well observed medical treatment. Patients are invited to give informed consent; the technic must be performed in an appropriate environment by an experienced physician. The initial treatment of back pain is medical. This pathology is multifactorial and the relief of symptoms is often incomplete. The patient should be urged to feel responsible for and involved in his treatment.

[Chronic pain management: a multidisciplinary approach]. / Prise en charge de la douleur chronique en equipe pluridisciplinaire.

Assessment of chronic pain is one of medicine's most difficult challenges. A structured and flexible multidisciplinary approach allows full characterisation of the various components of the pain syndrome. This then allows the use of a rational combination of pharmacologic, physical, psychological, and surgical techniques. It is essential to gain the patient's confidence, collaboration, and compliance. Patients can better manage their situation when their needs are clarified and when care is oriented toward concrete therapeutic objectives.

Antiresorptive drugs beyond bisphosphonates and selective oestrogen receptor modulators for the management of postmenopausal osteoporosis.

Osteoporotic fractures are a major cause of morbidity in the elderly population. Since postmenopausal osteoporosis is related to an increase in osteoclastic activity at the time of menopause, inhibitors of bone resorption have genuinely been considered an adequate strategy for prevention and treatment of osteoporosis. Bisphosphonates and selective oestrogen receptor modulators are widely prescribed to treat osteoporosis. However, other antiresorptive drugs have been developed for the management of osteoporosis, with the objective of providing a substantial reduction in osteoporotic fractures at all skeletal sites, combined with an acceptable long-term skeletal and systemic safety profile. Denosumab, a human monoclonal antibody to receptor activator for nuclear factor kappa B ligand, has shown efficacy against vertebral, nonvertebral and hip fractures. Its administration every 6 months as a subcutaneous formulation might significantly influence compliance and persistence to therapy. Additional results regarding long-term skeletal safety (i.e. osteonecrosis of the jaw and atypical diaphyseal femoral fracture) are needed. Odanacatib, a selective cathepsin K inhibitor, is a promising new approach to the inhibition of osteoclastic resorption, with the potential to uncouple bone formation from bone resorption. Results regarding its anti-fracture efficacy are expected in the coming months.