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.

[Effect of vitamin D deficiency on cardiovascular risk]. / Influence de la vitamine D sur le risque cardiovasculaire.

Vitamin D deficiency affects almost 50 % of the population worldwide. Besides its classical effects on bone and calcium metabolism, vitamin D displays a wide spectrum of non classical effects. Among these effects, those targeting the cardiovascular system are mostly documented by observational, experimental and small intervention trials that most often evaluated intermediate parameters. The time has now come for large placebo-controlled trials targeting clinical endpoints such as the incidence of major cardiovascular events and mortality.

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.

Hospitalized late preterm mild preeclamptic patients with mature lung testing: what are the risks of delivery?

OBJECTIVE: To evaluate the risk of elective delivery of hospitalized patients with isolated mild preeclampsia with mature fetal lung profile compared with a cohort of patients who had preeclampsia with indicated delivery matched for gestational age. STUDY DESIGN: Patients with mild preeclampsia requiring hospitalization between 34 and 37 weeks estimated gestational age were offered amniocentesis for assessment of fetal lung maturity. If fetal lung maturity was documented, patients were offered delivery. These cases were then compared with indicated or spontaneously delivered controls with preeclampsia matched for gestational age. RESULT: A total of 51 cases were identified and matched with 51 controls. Sixteen case neonates (31.4%) were admitted to neonatal intensive care unit compared with 21 controls (41.2%). Five cases (9.8%) in each group developed respiratory distress syndrome (RDS). CONCLUSION: Elective delivery of mild preeclampsia with mature lung profiles in the late preterm gestation is not without neonatal risks, including a 10% risk of RDS in this series.

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.

[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.

[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.

Strontium ranelate prevents quality of life impairment in post-menopausal women with established vertebral osteoporosis.

UNLABELLED: Strontium ranelate reduces the risk of fracture in post-menopausal osteoporotic women with prevalent fractures for whom quality of life is severely impaired. The SOTI study, which used the SF-36 questionnaire and disease-specific QUALIOST module, demonstrated that treatment with strontium ranelate improved osteoporotic women's quality of life compared with placebo. INTRODUCTION: The Spinal Osteoporosis Therapeutic Intervention (SOTI) study demonstrated the effect of orally administered strontium ranelate versus placebo on the incidence of new vertebral fractures and compared impact on quality of life (QoL). METHODS: QoL was assessed 6 monthly over 3 years using the QUALIOST and SF-36 questionnaires in post-menopausal osteoporotic women with prevalent fracture taking strontium ranelate or placebo 2 g/day. A total of 1,240 women were included (strontium ranelate: n=618 and placebo: n=622). RESULTS: The QUALIOST total score decreased in the strontium ranelate group, indicating preserved QoL compared with a deterioration in the placebo group (P=0.016). Strontium ranelate patients had reduced QUALIOST emotional and physical dimension scores (P=0.019 and 0.032, respectively, versus placebo), indicating beneficial effects on emotional and physical functioning. There was a trend towards better SF-36 scores in the strontium ranelate group, although there were no significant between-group differences. More strontium ranelate patients (+31%) were free from back pain over 3 years versus placebo (P=0.005), with a significant effect from the first year of treatment (P=0.023). CONCLUSION: Strontium ranelate has beneficial effects on QoL in women with post-menopausal osteoporosis compared with placebo.

A very high incidence of low 25 hydroxy-vitamin D serum concentration in a French population of patients with primary hyperparathyroidism.

Since the demonstration that vitamin D status might influence the clinical and biological expression of primary hyperparathyroidism (PHPT), a serum 25-hydroxy vitamin D (25-OHD) concentration of 50 nmol/l has been considered by an expert panel as the minimum level to be maintained in asymptomatic PHPT patients. Two yr after this recommendation, we aimed to evaluate the frequency of serum 25-OHD concentrations below this threshold in PHPT patients. In the present study, serum 25-OHD, second- and third-generation PTH, calcium, phosphate, magnesium, albumin and creatinine were measured in 72 out 145 consecutive PHPT patients operated on in our Endocrine Surgery Department, in whom blood samples were available before as well as two days after surgical intervention. Before surgery, the frequency of serum 25-OHD levels <50 nmol/l ranged from 91.5 to 100% whatever the classification used to identify patients: whole group, symptomatic vs asymptomatic, patients with calcium levels >3 vs <3 mmol/l. 25-OHD concentrations correlated negatively with the weight of adenoma, PTH levels, and total calcium concentrations measured before surgery. Pre-operative PTH levels, whatever the assay used, and total calcium concentrations were positively and significantly correlated. Two days post-surgery, 13 patients were moderately hypocalcemic. Neither pre-surgery 25-OHD nor PTH, calcium or phosphorus level or adenoma weight were predictive of post-operative hypocalcemia. The dramatic frequency of low 25-OHD concentrations in our PHPT patients demonstrates that the above-mentioned recommendation is far from being applied in France despite evidence of worsening expression of PHPT with decreasing 25-OHD serum levels.

[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.

[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.

Use of clinical risk factors in elderly women with low bone mineral density to identify women at higher risk of hip fracture: The EPIDOS prospective study.

Elderly women with very low bone mineral density (BMD) ( T-score