[How to prevent early postmenopausal fracture risk? Proposition of a strategy]. / Proposition d'une stratégie de prévention du risque fracturaire en début de ménopause.

Postmenopausal osteoporosis is a chronic disease, which justifies long-term treatment in those women with an increased risk of fracture. The current disponibility of various drugs, which have demonstrated their efficacy in reducing the incidence of fracture, has raised the question of the best treatment strategy in a woman who would begin her postmenopausal period with an increased risk for fracture. Indeed, for most treatments (with the exception of hormonal replacement therapy [HRT]), their efficacy in reducing the risk of fracture has been mainly demonstrated in higher risk elderly women (above 65 years) with prevalent vertebral fractures. There is uncertainty concerning their cost-effectiveness in younger women for a true primary prevention of the risk of fracture. Furthermore, current guidelines recommend a 5-year period of treatment which has led us to considering treatment strategies which would be based on various sequential treatment periods over time, the selection of each specific sequence being determined by the clinical situation of the woman, the level of her fracture risk and the expected skeletal (in terms of spectrum of bone effects) and potential extraskeletal benefits of drugs. In this regard, HRT or raloxifene, which allows a more global approach of the menopause-induced consequences of estrogen deficiency than the sole prevention of osteoporosis, should be privileged within the first 10 years of treatment or so in those youngest women at increased risk for subsequent fracture. Use of bisphosphonate or strontium ranelate should be thus reserved at a more advanced age, when the prevention of hip fracture becomes mandatory.

Bone mineral density at menopause does not predict breast cancer incidence.

UNLABELLED: In this prospective study in 2,137 perimenopausal and early postmenopausal women who were followed over a 13.1-year period of time, we observed no association between bone mineral density measured at the beginning of menopause and the subsequent risk of breast cancer. INTRODUCTION: This study aimed to investigate the relationship between BMD and the risk of breast cancer (BC) in young postmenopausal women. METHODS: As part of a clinical research program, 2,137 women who were perimenopausal or within their 5 first postmenopausal years were scanned between 1988-1990 and reviewed on average 13.1 years after their initial examination. Ninety-eight incident BC cases were recorded throughout the follow-up. RESULTS: Women with incident BC significantly differed from those who had never had BC with regard to age at menarche, age of birth of 1st child, familial history of BC and postmenopausal hormone therapy (PHT) use. There was no significant difference between the two groups for baseline DXA of the spine. There was a trend for BC cases for having lower femoral neck BMD compared to women without BC. However, women with low BMD were more likely to have taken PHT by the end of the study. In Cox multivariate analyses the relationship between BC risk and femoral neck BMD no longer existed. CONCLUSIONS: There was no relationship between BMD measured within the first postmenopausal years and the risk of BC, which makes unlikely the possibility of using BMD as a predictor factor for BC in early postmenopausal women.

Frailty, osteoporosis and hip fracture: causes, consequences and therapeutic perspectives.

OBJECTIVE: The aim of this review of the literature is to report the factors which both contribute to the frailty syndrome and increase hip fracture risk in the elderly. This work is the fruit of common reflection by geriatricians, endocrinologists, gynecologists and rheumatologists, and seeks to stress the importance of detection and management of the various components of frailty in elderly subjects who are followed and treated for osteoporosis. It also sets out to heighten awareness of the need for management of osteoporosis in the frail elderly. DESIGN: The current literature on frailty and its links with hip fracture was reviewed and discussed by the group. RESULTS: The factors and mechanisms which are common to both osteoporosis and frailty (falls, weight loss, sarcopenia, low physical activity, cognitive decline, depression, hormones such as testosterone, estrogens, insulin-like growth factor-I (IGF-I), growth hormone (GH), vitamin D and pro-inflammatory cytokines) were identified. The obstacles to access to diagnosis and treatment of osteoporosis in the frail elderly population and common therapeutic pathways for osteoporosis and frailty were discussed. CONCLUSION: Future research including frail subjects would improve our understanding of how management of frailty can can contribute to lower the incidence of fractures. In parallel, more systematic management of osteoporosis should reduce the risk of becoming frail in the elderly population.

[Hormone replacement therapy in postmenopausal women: all the treatments are not the same]. / Traitement hormonal chez les femmes ménopausées: tous les traitements sont-ils équivalents?

Different estrogens combined with various progestins, administered are used in hormone therapy (HT) for postmenopausal women. All these compounds, which do not have the same chemical structure and the same pharmacokinetic behavior as the bio-identicals hormones, estradiol 17beta and progesterone, have intrinsic properties which can lead to tangible differences in therapeutic results. Recent biological and clinical data strongly suggest that the coronary and venous thromboembolic risk as well as the breast cancer risk attributed to HT use would not be the same according to the therapeutic scheme used. This article will briefly review the general principle of a true "hormone replacement therapy" and will discuss the recent data supporting the hypothesis that the cardiovascular and breast cancer risks might be lower with bio-identical hormones than with other therapeutic schemes.

[Raloxifene in postmenopausal women]. / Indications du raloxifène chez la femme ménopausée.

Since the diffusion of the WHI's trial and MWS results, which reported a negative risk/benefit balance of hormone therapy, the management of postmenopausal women has deeply changed over the last 2-3 years. In particular, for the prevention of osteoporosis, the use of other efficient agents tends now to be more widely recommended rather than estrogens. The SERMs with raloxifene are new molecules that have estrogen agonist effects on bone and estrogen antagonist or neutral effects on endometrial and breast tissue. The efficacy of raloxifene to inhibit postmenopausal bone loss as well as to reduce the incidence of vertebral fractures has been demonstrated in women at high risk for osteoporosis through a large randomized placebo-controlled trial involving several thousands of postmenopausal women (MORE trial). Furthermore, the extraskeletal effects of raloxifene might represent an advantage for a global management approach of postmenopausal women, although to date, its exclusive indication is namely the prevention of osteoporosis. However, the estrogen antagonist effects of raloxifene on breast tissue as well as its good safety profile with regard to both the endometrium and the risk of heart diseases are likely to make raloxifene of particular interest for women around the age of 60 years old. Adverse events associated with raloxifene only included an increase in the absolute risk of venous thromboembolism in a comparable manner as with estrogen therapy. Also, its lack of efficacy in reducing hot flushes or preventing vaginal dryness may limit its use in young symptomatic postmenopausal women. Also, its lack of reimbursement in women with no prior fragility fracture must be taken into account.

Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International.

OBJECTIVES: Alendronate and raloxifene are antiresorptive agents with different mechanisms of action, each used to treat osteoporosis in postmenopausal women. This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density. DESIGN: Randomized, double-masked, double-dummy multicentre international study. SETTING: Clinical trial centres in Europe, South America and Asia-Pacific. SUBJECTS: A total of 487 postmenopausal women with low bone density, based on bone mineral density (BMD) of the lumbar spine or hip (T-score < or =-2.0). Interventions. Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months. MAIN OUTCOME MEASURES: Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting. RESULTS: Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months. Lumbar spine BMD increased 4.8% with alendronate vs. 2.2% with raloxifene (P < 0.001). The increase in total hip BMD was 2.3% with alendronate vs. 0.8% with raloxifene (P < 0.001). Reductions in bone turnover were significantly larger with alendronate than raloxifene. Overall tolerability was similar, however, the proportion of patients reporting vasomotor events was significantly higher with raloxifene (9.5%) than with alendronate (3.7%, P = 0.010). The proportion of patients reporting gastrointestinal events was similar between groups. CONCLUSION: In postmenopausal women with low bone density, improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene.

[Diagnostic value of classical neurophysiologic profile in various phenotypes of hereditary, pressure-sensitive neuropathies]. / Valeur diagnostique du profil neurophysiologique classique dans les différents phénotypes de la neuropathie héréditaire sensible à la pression.

PURPOSE: We looked for electrodiagnostic features that raise suspicion of hereditary neuropathy with liability to pressure palsies (HNPP). METHOD: A retrospective review of eight cases with confirmed histologic (one case) or chromosome 17 deletion (seven cases) analysis was performed. RESULTS: Autosomal dominant disease was present in 63% of the patients, 75% being men. Mean age at examination and at first symptom was 27 and 22 years respectively. Five patients have one or more acute nerve palsies, without residual deficit, but one presented sensory symptoms in internal saphena territory. Three patients had others phenotypes: a man presented with four episodes of facial palsy and one woman was asymptomatic; another patient with diabetes mellitus presented an associated chronic sensorimotor polyneuropathy. In agreement with other studies of HNPP we found in most patients a diffuse increase in distal motor latence, contrasting with normal or moderately decreased motor nerve conduction velocity, multiple electrophysiologic entrapment and diffuse reduction in sensory nerve action potential and/or velocity. However, this electrophysiological pattern was incomplete or masked in HNPP with cranial nerves palsies, in asymptomatic form of HNPP or in HNPP associated with polyneuropathy. CONCLUSION: These data confirm the clinical phenotypic heterogeneity of the 17p11.2 deletion and highlight the limits of the classic electrophysiological pattern in asymptomatic HNPP or associated with uncommon clinical features.

[Neuritic leprosy disclosed by reversal reaction]. / Neuropathie lépreuse révélée par une réaction de réversion.

We report a case of neuritic borderline tuberculoid leprosy with lingering insidious growth disclosed by a brutal reversal reaction. Inflammatory polyarthralgia and sensory and motor loss in the median and ulnar territories, without skin lesions, suggested vasculitis. A few weeks later, inflammatory skin lesions developed leading to the diagnosis of biopsy proven leprosy. Leprosy should be considered as a possible diagnosis in patients with multineuritis, especially when associated with rheumatic or cutaneous manifestations. Early skin biopsy in neuritic leprosy is discussed.

[Muscular exercise intolerance syndrome in Becker muscular dystrophy]. / Place du syndrome d'intolérance musculaire à l'exercice dans la dystrophie musculaire de Becker.

OBJECTIVE: To determine whether exertional muscle pain syndrome (EMP) is a benign phenotype or an early stage of Becker-type muscular dystrophy (BMD). METHODS: Muscle dystrophin analysis led to the diagnosis of BMD in 6 patients complaining of EMP. RESULTS: Three patients had a history of X-linked inheritance and age at clinical onset was 4 to 11 years in five, and one patient had a later onset aged 23. Pseudohypertrophy of the calf muscles was absent in one patient, but all had experienced mild (5/6) pelvic weakness and (or) atrophy one to 17 years after the onset. High serum CK level was present (X 14). Normal anti-dystrophin immunostaining in two cases did not rule out the diagnosis that was only made made by Western blot analysis or genetic studies. All exhibited in-frame deletions (exons 45-48) within the dystrophin gene. CONCLUSION: The 36 patients with BMD-EMP analysed in the literature, exhibited different deletions and no worsening in 66.7% of cases. Western blot was more precise than immunolabelling with 96.8% positivity versus 70.5%. Dystrophin analysis by Western blot and (or) DNA analysis should be included in the evaluation of patients with EMP syndrome without deficient muscle energy metabolism, particularly those with pseudohypertrophy of the calf muscles or high serum CK levels.

[Anterior compartment syndrome of the forearm caused by exercise: unusual cause of recurrent episodes of acute effort rhabdomyolysis]. / Le syndrome de loge antérieure de l'avant-bras provoqué par l'exercice: une cause rare d'épisodes récidivant de rhabdomyolyse aiguë d'effort.

INTRODUCTION: An effort-related compartmental syndrome is well known in the leg, but may be present infrequently, acutely or chronically in the anterior compartment of the forearm. EXEGESIS: We report a case of a 32-year-old man who presented four times after climbing exercises a bilateral compartment of the forearm, unusual because of the observation of rhabdomyolysis, but without irreversible damage. Clinical information and follow-up on two acute and 14 chronic cases were reexamined, showing a homogenous presentation. He refused fasciotomy because he stopped athletic activities. Measurement of intramuscular pressure after exertion was useful for diagnosis. CONCLUSION: A local effort-related pain must call to mind a chronic compartment syndrome of the forearm, which may risk incurring the acute form, with irreversible lesions of muscle and nerve, and possibly renal failure because of rhabdomyolysis.

[Recurrent rhabdomyolysis revealing chronic exertional compartment syndrome of the biceps]. / Episodes récidivants de rhabdomyolyse révélant un syndrome de loge antérieure du bras provoqué par lexercice.

UNLABELLED: OBJECTIVE AND PATIENT: To report, an uncommon case of recurrent effort-related biceps compartment syndrome induced by strengthening exercises (body building) in a thirty-years-old white man. DISCUSSION-CONCLUSION: compartment syndrome is typically observed in the lower leg or in the forearm with pain, muscle tightness, cramp-like feeling during exertion. The involvement of the biceps was only described after traumatisms. Patient was initially thought to have metabolic myopathy because acute episodes of exercise induced myalgia and elevated serum CK. Tissue pressure monitoring prior and after a standard exercise test is helpful for diagnosing the recurrent form. The only alternative to fasciotomy is to stop sports activities.

Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women.

This study aimed to assess the changes in vertebral bone mineral density (BMD) after cessation of hormone replacement therapy (HRT) in postmenopausal women who had been treated on a long-term basis. Fifty healthy postmenopausal women who had been followed both during the course of HRT and after cessation of treatment in our menopause clinic were included in this study. All women had started HRT within the first 3 years after the postmenopause and had received HRT (either 1.5 mg/day of 17 beta-estradiol given percutaneously or 50 micrograms/day of 17 beta-estradiol given as a transdermal patch, combined in all women with natural progesterone or a 19-norprogesterone derivative) for a mean 5 +/- 2.4 years. In all women, vertebral BMD was assessed during the course of HRT up to the last 6 months before estrogen withdrawal, then at least once within the first 18 months after cessation of treatment. Of the initial population, 30 women were additionally reviewed later on and up to 8 years after cessation of treatment (mean duration of follow-up for the whole population: 3.9 +/- 1.7 years). Rates of changes in vertebral BMD were compared with those determined in a group of healthy untreated women who had been followed within the first years of postmenopause during the same time period as the study population. In the study group, bone loss was found to accelerate within the first 2 years after HRT withdrawal and the annual rate of loss was identical to that which occurs within the first 2 years of postmenopause in untreated women (-1.64% +/- 1.3% vs -1.52 +/- 0.9%, NS). Beyond this first 2-year time period, the annual rate of bone loss decreased as a function of time following cessation of treatment, as was observed following the menopause in untreated women (between 3 and 5 years: -0.83% + 1.35% in the study group vs -0.70% +/- 0.8% in the control group, NS). On average, 3 years after cessation of HRT mean vertebral BMD when expressed as a Z-score was significantly higher (-0.13 vs -0.89, p < 0.01) than at baseline, before HRT was started, which suggested a lasting beneficial effect on bone mass. However, even though our findings do not support the hypothesis that bone loss might continue to be accelerated several years after cessation of treatment we cannot fully address the question as to whether any residual benefit on bone mass over a longer period of time may be observed. In conclusion, the pattern of bone loss observed after cessation of estrogen therapy was found to be comparable to that which occurs in younger women within the first years after the menopause. Such a pattern needs to be kept in mind when the decision to stop HRT is taken, especially in women who were given HRT to prevent osteoporosis. The issue of assessing their risk of fracture several years after cessation of treatment thus needs to be addressed.

Ability of peripheral DXA measurements of the forearm to predict low axial bone mineral density at menopause.

The aim of this study was to evaluate the ability of peripheral dual-energy X-ray absorptiometry (pDXA) measurement of the forearm to predict low axial bone mineral density (BMD) as defined according to the WHO classification. Two hundred and thirty-four healthy women aged 45-60 years were investigated. BMD was measured at the proximal and distal radius + ulna by pDXA and at the lumbar spine and femoral neck by DXA. There was a significant but moderate correlation between peripheral and axial BMD measurements, with r values ranging from 0.4 to 0.6 (SEE: 13.5-17%). The cutoff values for the proximal and distal radius BMD that allow the identification with 95% sensitivity of postmenopausal women with either a lumbar spine or femoral neck T-score < -1, corresponded to a T-score of +0.5 (proximal radius) and +1 (distal radius). More than 90% of the whole population had a peripheral T-score below these thresholds. Using an axial T-score < or = -2.5 as the definition of abnormality reduced to 48% (proximal radius) to 66% (distal radius) the number of women who would have required DXA axial measurements (i.e., with a pDXA T-score below the cutoff value of -0.7). Of the 33 women (14%) with a proximal radius T-score < or = -2.5 (osteoporosis), only 1 had a lumbar spine and femoral neck T-score > or = -1 (normal). Conversely, of the 50% (proximal radius) to 65% (distal radius) of the women with normal forearm measurement, 5% (proximal radius) to 9% (distal radius) were found to be osteoporotic and an additional 57% (proximal radius) to 59% (distal radius) could be classified as osteopenic (T-score between -1 and -2.5) at either the lumbar spine or femoral neck. In conclusion, use of pDXA forearm measurement as a prescreening tool in early postmenopausal women should allow the direct identification of about 50% of the women with no axial osteoporosis. However, this study highlights the difficulties in using a unique T-score that could be applied to different sites to diagnose osteoporosis.

[Transformation of mycosis fungoides to pleomorphic T-cell lymphoma and central nervous system involvement]. / Mycosis fongoïde avec transformation en un lymphome cutané pléiomorphe et localisation secondaire cérébrale.

INTRODUCTION: Although mycosis fungoides is a malignant T-cell lymphoma involving mainly the skin, neurological complications are possible, with a poor prognosis. EXEGESIS: A 59-year-old man, treated for mycosis fungoides with transformation to a pleomorphic T-cell lymphoma for 1 year, was seen for mental status changes with confusion. A brain parenchyma localisation was found. CONCLUSION: This observation emphasizes the exceptional neurological tropism in the patients with mycosis fungoides. A transformation to a more aggressive cutaneous T-cell lymphoma seems necessary to induce a central nervous system involvement.

[Multiple intracranial and intraspinal meningiomas successively discovered in the absence of neurofibromatosis: 2 cases]. / Méningiomes multiples intracrânien et intrarachidien de découverte successive en l'absence de neurofibromatose: deux observations.

Multiple meningiomas in different neuroaxial compartments are quite rare. We describe the case of a 44-year-old woman who developed three intracranial meningiomas and 8 years later a T3 dorsal meningioma. Histologically, the frontal and dorsal tumors appeared as benign psammomatouss meningiomas. Both tumors were removed successfully. The second patient was a 31-year-old woman who developed right benign fronto-parietal transitional meningioma. She presented local and spheno-orbital recurrences, then a lombo-sacral lesion. The histological picture worsened from benign to malignant with multiple recurrences. Several mechanisms could account for multiple meningiomas. Such meningiomas could arise from a single primary tumor via subarachnoidal spread of a benign or malignant nature. Alternatively, they could be atypical forms of neurofibromatosis type 2 or tumors with a multifocal origin.

[Estrogens and selective estrogen receptor modulators in the treatment of osteoporosis]. / Estrogènes et modulateurs spécifiques des récepteurs estrogéniques dans le traitement de l'ostéoporose.

Estrogen deficiency is the major determinant of bone loss, not only in the first years postmenopause, but also throughout the entire life and in the elderly. Major progress in the knowledge of cellular actions of estrogens has been made leading to a better understanding of the underlying mechanisms of different estrogen-deficiency related diseases such as osteoporosis, atherosclerosis and also maybe cerebral aging. Estrogen replacement therapy remains the first choice treatment in the prevention of postmenopausal osteoporosis, but the continuous aging process of the female population raises the question of a better strategy of action in a more efficient prevention of hip fractures. Moreover, the potential gynecological effects of estrogens are likely to limit their indications or long-term use. The development of new compounds, called SERMs (selective estrogen receptor modulators), with both agonist and antagonist estrogen actions, in particular with no negative effects on the uterus and the breast opens new therapeutical insights into the prevention of postmenopausal osteoporosis.