Multiple brown tumors: a bone complication due to long-term untreated pseudohypoparathyroidism.

Bone lytic lesions are a possible complication of pseudohypoparathyroidism type 1B, in undertreated adult patients. Whole body [18F] F-fluorocholine PET/CT is a useful imaging tool to assess brown tumor progression in this context. We describe the case of a 33-year-old woman, referred for the diagnostic evaluation of lytic bone lesions of the lower limbs, in the context of asymptomatic pseudohypoparathyroidism. She had been treated with alfacalcidol and calcium during her childhood. Treatment was discontinued at the age of 18 years old because of the lack of symptoms. A femur biopsy revealed a lesion rich in giant cells, without malignancy, consistent with a brown tumor. Laboratory tests showed a parathyroid level at 1387 pg/ml (14-50). Whole-body Fluorocholine PET/CT revealed hypermetabolism of bone lesions. The final diagnosis was brown tumors related to hyperparathyroidism complicating an untreated pseudohypoparathyroidism. Genetic testing confirmed PHP type 1B. Pseudohypoparathyroidism with radiographic evidence of hyperparathyroid bone disease, is a very rare condition due to parathyroid hormone resistance in target organs, i.e., kidney resistance, but with conserved bone cell sensitivity. It has been reported in only a few cases of pseudohypoparathyroidism type Ib. Long-term vitamin D treatment was required to correct bone hyperparathyroidism. With this rationale, the patient was treated with calcium, alfacalcidol, and cholecalciferol. One-year follow-up showed complete resolution of pain, improvement in serum calcium, and regression of bone lesions on [18F]F-fluorocholine PET/CT. This case illustrates the usefulness of [18F]F-fluorocholine PET/CT for the imaging of brown tumors in pseudohypoparathyroidism type 1B, and emphasizes the importance of calcium and vitamin D treatment in adult patients, to avoid the deleterious effects of high parathyroid hormone on skeletal integrity.

Pregnancy-related fractures: a retrospective study of a French cohort of 52 patients and review of the literature.

A retrospective, multicentre study involving 52 patients was carried out to define the causes and characteristics of pregnancy-related osteoporosis. The mean number of vertebral fractures occurring during the last trimester of pregnancy or at the time of delivery was 3.8. This is often promoted by risk factors before or during pregnancy. INTRODUCTION: In order to define the causes or predisposing factors of pregnancy-related osteoporosis and its clinical, radiological and bone density characteristics, laboratory findings, course and outcome, we carried out a retrospective multicentre study. METHODS: The records of 52 women hospitalised over the last 10 years in the rheumatology departments of six French university hospitals and with a diagnosis of pregnancy-related osteoporosis were examined. RESULTS: The patients' mean age at time of fracture was 32.1 years. In 10 patients, the fractures had occurred during the last trimester of pregnancy, and in 36 at the time of delivery or during the first 2 months post-partum. The mean number of vertebral fractures was 3.8 ± 2.0. Thirty three of the 52 patients had a risk factor of low bone mass before pregnancy. Twelve had disorders or treatments (heparin) that might promote osteoporosis during pregnancy, while 14 had no trigger factors before or during pregnancy. Overall, phosphate and calcium levels were normal, except for hyperphosphoraemia in lactating women (90%). On DXA scan, osteoporosis predominated in the trabecular bone (spinal T-score - 3.4, hip T-score - 2). Only 10 patients had a repeat fracture, and the increase in bone mineral density during follow-up was considerable, and improved by bisphosphonates (annual gain + 10% in the spine) or teriparatide (+ 15%). CONCLUSIONS: Pregnancy-related osteoporosis gives rise to multiple vertebral fractures. It is often promoted by risk factors before or during pregnancy. Its mechanism is still unknown. Treatment with bisphosphonates or teriparatide appears to improve the recovery of bone mineral density.

How the reference values for serum parathyroid hormone concentration are (or should be) established?

Well-validated reference values are necessary for a correct interpretation of a serum PTH concentration. Establishing PTH reference values needs recruiting a large reference population. Exclusion criteria for this population can be defined as any situation possibly inducing an increase or a decrease in PTH concentration. As recommended in the recent guidelines on the diagnosis and management of asymptomatic primary hyperparathyroidism, PTH reference values should be established in vitamin D-replete subjects with a normal renal function with possible stratification according to various factors such as age, gender, menopausal status, body mass index, and race. A consensus about analytical/pre-analytical aspects of PTH measurement is also needed with special emphasis on the nature of the sample (plasma or serum), the time and the fasting/non-fasting status of the blood sample. Our opinion is that blood sample for PTH measurement should be obtained in the morning after an overnight fast. Furthermore, despite longer stability of the PTH molecule in EDTA plasma, we prefer serum as it allows to measure calcium, a prerequisite for a correct interpretation of a PTH concentration, on the same sample. Once a consensus is reached, we believe an important international multicentre work should be performed to recruit a very extensive reference population of apparently healthy vitamin D-replete subjects with a normal renal function in order to establish the PTH normative data. Due to the huge inter-method variability in PTH measurement, a sufficient quantity of blood sample should be obtained to allow measurement with as many PTH kits as possible.

Individual site-specific bone mineral density gain in normocalcemic primary hyperparathyroidism.

UNLABELLED: In this study, we show that successful parathyroidectomy is followed at 1 year by a significant individual bone mineral density (BMD) gain in nearly half of normocalcemic PHPT patients with reduced bone mass. Alkaline phosphatase levels above median were identified as an independent predictor of individual BMD gain in normocalcemic PHPT patients. INTRODUCTION: The aims of this study were to assess bone mineral density (BMD) gains after parathyroidectomy (PTX) in normocalcemic primary hyperparathyroidism (PHPT) at the individual level and to identify predictors of BMD gain after PTX in this context. METHODS: Longitudinal cohort study of 55 PHPT patients referred for low bone mass and mild abnormalities of calcium/phosphorus metabolism, and successfully treated by PTX. BMD gain at 1 year was considered significant if ≥0.030 g/cm(2) at one site or more, without any equivalent BMD loss at another site. A logistic regression analysis was performed to identify predictive factors of individual BMD gain. RESULTS: Among the 55 PHPT patients included, 29 patients with hypercalcemia, 36 patients with normocalcemic PHPT, defined by normal pre-PTX serum total (albumin-corrected) calcium (tCa), including 15 patients with normal ionized calcium (iCa), were identified. At 1 year of PTX, an individual BMD gain was observed in 73.7 % of hypercalcemic, 44.4 % of normocalcemic, and 46 % of PHPT patients with both normal tCa and iCa. Site-specific BMD gains were most important at the spine and hip in all subgroups including patients with normal iCa. Alkaline phosphatase activity above median, which reflects high bone turnover, was predictive of individual BMD gain, both in the overall cohort (OR = 4.9, 95 % CI 1.3-18.9), and in the normocalcemic group: OR = 8.4, 95 % CI 1.4-56.6. CONCLUSIONS: Successful PTX is followed at 1 year by a significant individual BMD gain in nearly half of normocalcemic PHPT patients with osteoporosis. ALP levels above median could contribute to the therapeutic decision in this context.

Is bone microarchitecture status of the lumbar spine assessed by TBS related to femoral neck fracture? A Spanish case-control study.

UNLABELLED: Bone mineral density (BMD) as assessed by dual energy X-ray absorptiometry (DXA) constitutes the gold standard for osteoporosis diagnosis. However, DXA does not take into account bone microarchitecture alterations. INTRODUCTION: The aim of our study was to evaluate the ability of trabecular bone score (TBS) at lumbar spine to discriminate subjects with hip fracture. METHODS: We presented a case-control study of 191 Spanish women aged 50 years and older. Women presented transcervical fractures only. BMD was measured at lumbar spine (LS-BMD) using a Prodigy densitometer. TBS was calculated directly on the same spine image. Descriptive statistics, tests of difference and univariate and multivariate backward regressions were used. Odds ratio (OR) and the ROC curve area of discriminating parameters were calculated. RESULTS: The study population consisted of 83 subjects with a fracture and 108 control subjects. Significant lower spine and hip BMD and TBS values were found for subjects with fractures (p < 0.0001). Correlation between LS-BMD and spine TBS was modest (r = 0.41, p < 0.05). LS-BMD and TBS independently discriminate fractures equally well (OR = 2.21 [1.56-3.13] and 2.05 [1.45-2.89], respectively) but remain lower than BMD at neck or at total femur (OR = 5.86 [3.39-10.14] and 6.06 [3.55-10.34], respectively). After adjusting for age, LS-BMD and TBS remain significant for transcervical fracture discrimination (OR = 1.94 [1.35-2.79] and 1.71 [1.15-2.55], respectively). TBS and LS-BMD combination (OR = 2.39[1.70-3.37]) improved fracture risk prediction by 25 %. CONCLUSION: This study shows the potential of TBS to discriminate subjects with and without hip fracture. TBS and LS-BMD combination improves fracture risk prediction. Nevertheless, BMD at hip remains the best predictor of hip fracture.

Relationship between 3-month changes in biochemical markers of bone remodelling and changes in bone mineral density and fracture incidence in patients treated with strontium ranelate for 3 years.

SUMMARY: From two randomised controlled trials, it is shown that 3-month changes in biochemical markers of bone formation (bone-specific alkaline phosphatase and C-terminal propeptide of type I procollagen) were associated with 3-year bone mineral density (BMD) changes, but not fracture incidence in patients treated with strontium ranelate. INTRODUCTION: The purpose of this study was to assess if short-term change in biochemical markers of bone remodelling is associated with long-term BMD change and fracture incidence observed during treatment with strontium ranelate. METHODS: From the SOTI and TROPOS trials, bone-specific alkaline phosphatase (BALP), C-terminal propeptide of type I procollagen (PICP), serum C-terminal telopeptides (S-CTX) and urine N-terminal telopeptides of type I collagen (U-NTX) were assessed at baseline and after 3 months. RESULTS: Two thousand three hundred seventy-three women were included in this study. Multiple regression analysis showed that 3-month changes in PICP and BALP but not s-CTX I nor s-NTX I were significantly (p < 0.001) associated with 3-year BMD changes at the lumbar spine and the femoral neck. Changes in s-CTX I, PICP and BALP were significantly associated with change in total proximal femur BMD. Changes in biochemical markers explain less than 8% of the BMD changes. The 3-month changes in BALP, PICP s-CTX I and s-NTX I were not significantly associated with fracture incidence. CONCLUSIONS: Short-term changes in biochemical markers of bone formation are associated with future BMD changes in patients treated with strontium ranelate, suggesting a bone-forming activity of this treatment, but are not appropriate to monitor the efficacy of strontium ranelate at the individual level.

Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis.

SUMMARY: Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. CONCLUSION: In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.

[Recommendations for the management of bone demineralization in cystic fibrosis]. / Recommandations pour la prise en charge de la déminéralisation osseuse dans la mucoviscidose.

A high prevalence of low bone mineralization is documented in adult patients with cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients and osteoporosis in 13 to 57% of them. In children, studies are discordant probably because of different control database. Denutrition, inflammation, vitamin D and vitamin K deficiency, altered sex hormone production, glucocorticoid therapy, and physical inactivity are well known risk factors for poor bone health. Puberty is a critical period and requires a careful follow-up for an optimal bone peak mass. This review is a consensus statement established by the national working group of the French Federation of CF Centers to develop practice guidelines for optimizing bone health in patients with CF. Recommendations for screening and for calcium, vitamin D and K supplementation are given. Further work is needed to define indications for treatment with biphosphonates and anabolic agents.

[Update on vitamin D and evaluation of vitamin D status]. / Actualité sur les effets de la vitamine D et l'évaluation du statut vitaminique D.

Knowledge about vitamin D has greatly improved during the last few years. Vitamin D cannot any more be considered as exclusively necessary to prevent ricket/osteomalacia. Its role in the prevention of some osteoporotic fractures in the elderly (in association with calcium nutrition) is now well demonstrated and many epidemiologic and laboratory data argue for a role in the prevention of several diseases or anomalies (cancer, auto-immune diseases, cardiovascular events, sarcopenia...). A few intervention studies confirming some of these effects also exist. Vitamin D status can easily be assessed by measuring serum 25 hydroxy vitamin D (25OHD) level. However, many experts have claimed that the population-based reference values for 25OHD are too low and that the cut-off value below which vitamin D insufficiency can be present is somewhere between 20 and 40 ng/mL with a clear tendency to target values above 30 ng/mL (75 nmol/L). The main consequences are that vitamin D insufficiency is highly frequent whereas the currently recommended supplementation doses are not sufficient.

[New definition of optimal vitamin D status and redefening serum parathyroid hormone reference range]. / Nouvelles définitions de l'insuffisance vitaminique D, retentissement sur les normes de PTH.

SCOPE: Knowledge concerning vitamin D has greatly improved during the past few years. Vitamin D can no longer be considered only as a preventive therapy for rickets-osteomalacia. Indeed, beside its role in the prevention of osteoporotic fractures in the elderly, many data suggest that it may be involved in the prevention of various diseases including cancers and auto-immune diseases. CURRENT SITUATION AND SALIENT POINTS: Vitamin D status may be easily assessed by the measurement of 25OHD serum concentration. However, many specialists in the field regard most 25OHD reference values as being too low, and believe that the 25OHD threshold below which vitamin D status can be considered as insufficient is somewhere between 50 and 100 nmol/L (20 to 40 ng/mL). It then appears that usually recommended amounts of supplemental vitamin D may be too low to reach these 25OHD concentrations, and thus need to be revised. We have proposed that PTH reference values should be established in healthy subjects with a normal vitamin D status. This supposes that 25OHD is measured in the reference population beforehand, and that the subjects with vitamin D insufficiency are eliminated from the reference group. PERSPECTIVES: Although more complicated than the usual way to establish normative data, we have shown that it decreases the upper limit of normal by 25-35%, enhancing thus the diagnostic sensitivity for hyperparathyroidism without a decrease in specificity.

Malignant transformation of primary chicken spleen cells by human transcription factor c-Rel.

Rel/NF-kappaB transcription factors control a variety of cellular processes, such as cell growth and apoptosis, that are relevant to oncogenesis, and mutations in genes encoding Rel/NF-kappaB transcription factors have been found in several human lymphoid cell cancers. In this study, we have used a sensitive cell outgrowth assay to demonstrate that wild-type human c-Rel can malignantly transform primary chicken spleen cells, and that transformation by c-Rel is accelerated by co-expression of Bc1-2. Full-length mouse c-Rel can also transform chicken spleen cells. These results are the first demonstration of a lymphoid cell malignant transforming ability for mammalian Rel/NF-kappaB transcription factors, and implicate c-Rel as a molecular target for cancer therapeutics.

Cultured circulating mononuclear cells from osteopetrotic infants express the osteoclast-associated vitronectin receptor and form multinucleated cells in response to 1,25-dihydroxyvitamin D3.

Malignant osteopetrosis is characterized by impaired osteoclast activity. Osteoclasts derive from hematopoietic stem cells. In osteopetrosis, marrow cavities fail to develop, resulting in extramedullary hematopoiesis and the presence of stem cells in the bloodstream. Resistance to 1,25-(OH)2D3 may be involved in the pathogenesis of the disease. Sensitivity to 1,25-(OH)2D3, calcitonin sensitivity, and expression of the osteoclast-associated vitronectin receptor (VR) was examined in cultures of circulating mononuclear cells of seven osteopetrotic infants (1.5-6 months old). Since peripheral blood from age-matched children contains few stem cells, umbilical cord blood was used as control. Mononucleated cells were isolated by the Ficoll-Hypaque method and cultured (10(6) cells per ml) in alpha-MEM containing 20% horse serum in presence or absence of added 1,25-(OH)2D3. VR was identified by immunochemical staining with MAb 23C6. 1,25-(OH)2D3 at 10(-8) M significantly stimulated the formation of multinucleated cells (MNC) in cultures from all osteopetrotic patients and cord blood samples. Cells from three of five patients responded to 10(-9) M 1,25-(OH)2D3, the minimal stimulatory concentration for cord blood. Salmon calcitonin (100 ng/ml) partially inhibited the 10(-8) M 1,25-(OH)2D3-induced MNC formation in cultures from three of six patients and in cultures of all cord blood samples. In both types of cultures mononuclear cells and MNC cross-reacted with MAb 23C6, and 1,25-(OH)2D3 concentration did not influence the number and percentage of these cells. This study does not support the hypothesis of 1,25-(OH)2D3 resistance in osteopetrotic infants and shows that mononuclear cells expressing VR, possibly osteoclast progenitors, develop in cultures of circulating mononuclear cells from these infants. 1,25-(OH)2D3 may not be closely involved in VR expression.

Mineral metabolism in infants with malignant osteopetrosis: heterogeneity in plasma 1,25-dihydroxyvitamin D levels and bone histology.

A group of 16 infants, 2 weeks to 11 months old, with malignant osteopetrosis were investigated to examine their vitamin D metabolism and parathyroid function. Bone biopsies from 6 children were studied by light microscopic histomorphometry and by electron microscopy. Considerable heterogeneity existed among the patients with respect to the parameters reflecting mineral metabolism and with respect to the histological manifestations of the disease. The most constant findings were as follows. Immunoreactive parathyroid hormone (iPTH) was elevated in all children, except in 1 patient who had tubular acidosis, and plasma calcium was low or normal, suggesting skeletal resistance to PTH. Plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] was not constantly elevated and appeared to depend on plasma phosphorus, as both parameters were negatively correlated (r = 0.704, p less than 0.01). Osteoblast activity, as evaluated by circulating alkaline phosphatase and osteocalcin and osteoblast number, measured for 6 children by bone histology, were not increased, despite hyperparathyroidism, suggesting PTH resistance or defective osteoblasts. Osteoclasts could be detected in 5 of the 6 children who had a biopsy. Osteoclast number (5.7-13.3% of bone surface) was normal or mildly increased, and marrow spaces were relatively well developed in 4 patients, whereas 1 child had markedly increased osteoclast number (28.3% of bone surface) and reduced marrow cavities. These 5 children received transplants, and engraftment occurred in all, except in the "hyperosteoclastic" patient. Further studies are necessary to establish the prognostic significance of this histologic feature.

Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study.

Increased bone turnover has been suggested as a potential risk factor for osteoporotic fractures. We investigated this hypothesis in a prospective cohort study performed on 7598 healthy women more than 75 years of age. One hundred and twenty-six women (mean years 82.5) who sustained a hip fracture during a mean 22-month follow-up were age-matched with three controls who did not fracture. Baseline samples were collected prior to fracture for the measurement of two markers of bone formation and three urinary markers of bone resorption: type I collagen cross-linked N- (NTX) or C-telopeptide (CTX) and free deoxypyridinoline (free D-Pyr). Elderly women had increased bone formation and resorption compared with healthy premenopausal women. Urinary excretion of CTX and free D-Pyr, but not other markers, was higher in patients with hip fracture than in age-matched controls (p = 0.02 and 0.005, respectively). CTX and free D-Pyr excretion above the upper limit of the premenopausal range was associated with an increased hip fracture risk with an odds ratio (95% confidence interval) of 2.2 (1.3-3.6) and 1.9 (1.1-3.2), respectively, while markers of formation were not. Increased bone resorption predicted hip fracture independently of bone mass, i.e., after adjustment for femoral neck bone mineral density (BMD) and independently of mobility status assessed by the gait speed. Women with both a femoral BMD value of 2.5 SD or more below the mean of young adults and either high CTX or high free D-Pyr levels were at greater risk of hip fracture, with an odds ratio of 4.8 and 4.1, respectively, than those with only low BMD or high bone resorption. Elderly women are characterized by increased bone turnover, and some markers of bone resorption predict the subsequent risk of hip fracture independently of hip BMD. Combining the measurement of BMD and bone resorption may be useful to improve the assessment of the risk of hip fracture in elderly women.

Vitamin D status and redefining serum parathyroid hormone reference range in the elderly.

Subclinical vitamin D insufficiency is characterized by mild secondary hyperparathyroidism and enhanced risk of osteoporotic fracture. However, although low levels of 25-hydroxyvitamin D (25OHD) are common in otherwise normal elderly people, vitamin D status has not generally been taken into account in the previously published reference values for serum PTH. We measured fasting morning serum (obtained from April through June) PTH, total calcium, albumin, phosphate, creatinine, bone markers, and 25OHD in 280 healthy subjects (140 men and 140 women), aged 60-79 yr. Serum PTH was measured by means of 2 immunoradiometric assays, the Allegro intact PTH assay (Nichols Institute Diagnostics) and the new CAP assay (Scantibodies Laboratory, Inc.). We found a high prevalence (167 of 280; 59.6%) of low 25OHD (< or =30 nmol/L) in these otherwise healthy individuals. The PTH concentrations (95% confidence interval) obtained in the whole group of 280 subjects ranged from 13-64 ng/L for the Allegro assay and from 10-44 ng/L for the CAP assay. In the subjects with a serum 25OHD concentration greater than 30 nmol/L, values for both PTH assays were lower, 10-46 and 9-34 ng/L for the Allegro and the CAP assays, respectively. By using these values as a reference range, approximately 25% of the subjects with a serum 25OHD level of 30 nmol/L or less had a high serum PTH level (whatever the assay), reflecting secondary hyperparathyroidism. This might be missed if the reference PTH values are those obtained in the entire group, as is usually done. These results strongly suggest that vitamin D status should be taken into account when establishing reference values for serum PTH in elderly subjects.

DHEA in bone and joint diseases.

Serum concentrations of dehydroepiandrosterone (DHEA) and its sulfate ester (sDHEA) decrease dramatically with age in parallel with the appearance of age-related health problems, leading to the suggestion that DHEA replacement therapy may be beneficial in older patients. Daily oral doses that restore sDHEA levels to the values seen in young adults are well tolerated in the short-term (6 months to 1 year) and seem to have a positive although modest beneficial effect on bone in elderly women, particularly those with low pretreatment sDHEA levels. This effect seems ascribable to both decreased bone resorption and increased bone formation, which are probably related mainly to conversion of DHEA into active sex steroids, i.e., estradiol and testosterone; this explains why there is no effect on bone in men, whose testes continue to produce testosterone throughout life. Other mechanisms of action, including an increase in insulin growth factor-1, may be operative also. DHEA cannot be recommended as a treatment for osteoporosis at present given the absence of studies evaluating possible efficacy in reducing the fracture rate and possible long-term side effects.

[Calciotropic hormones in rheumatology]. / Hormones calciotropes en rhumatologie.

Calcium homeostasis maintenance is controlled by calciotropic hormones action. Bone is a major target tissue for PTH and calcitriol. Excess in at least one of two hormones may be deleterious to bone, leading to osteoporosis. Calciotropic hormones must of course be measured if an anomaly of serum calcium/phosphate is discovered. However, when the degree of osteopenia is discordant with the risk factors of osteoporosis in a given patient, it may be of value to measure calciotropic hormones, even if serum calcium/phosphate are normal. Previously undiscovered cause(s) for secondary osteoporosis may be diagnosed which, if untreated, may impair the efficacy of antiresorptive treatments (estrogens, biphosphonates, ...). Whether to measure calciotropic hormones or not in other less-defined groups of osteoporotic patients remains both debatable and debated.

[Hyperparathyroidism and osteoporosis]. / Hyperparathyroïdie et ostéoporose.

INTRODUCTION: In patients with primary hyperparathyroidism, a definite diagnosis is the first step in the management strategy and relies on appropriately selected and carefully interpreted laboratory tests. Parathyroid hormone assays are being increasingly performed as part of the routine evaluation of osteoporosis. CURRENT KNOWLEDGE AND KEY POINTS: In this setting, laboratory tests are often consistent with primary hyperparathyroidism but should be interpreted with caution. FUTURE PERSPECTIVES: Bone mineral density measurements are useful for assessing the impact of primary hyperparathyroidism. The recommended bone mineral density cutoffs for selecting patients requiring parathyroidectomy were lowered in 2003, and the number of surgically treated patients has increased as a result. Parathyroidectomy remains the treatment of choice given the low mortality associated with this procedure and the absence of pharmacological alternatives suitable for long-term use.

[Approach of menopause in women at risk for breast cancer]. / Approche de la ménopause chez la femme à risque de cancer du sein.

The small but significant increase in risk of discovering breast cancer in women with hormone replacement therapy and the recent discussion of coronary benefit of this treatment have led many authors to insist on the necessity to evaluate the benefit/risks ratio before administration. This evaluation is particularly important for women that are already at high risk of breast cancer because of some genetic predisposition, family history or some benign breast diseases. In these cases, it is important to evaluate the absolute risk of breast cancer, to define the patient's needs more precisely, to specify menopausal symptoms; it is also important to evaluate the risk of osteoporosis, to review the various therapeutic possibilities, which are not only estrogen/progestin treatments (there are alternative treatments), and to give the patients honest information. Before obtaining the results of current trials, we are proposing here a pragmatic attitude and a decision algorithm to adopt a therapeutic attitude more easily which will be decided together by both patients and their physicians.