Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis.

PURPOSE: Atypical sub-trochanteric and femoral shaft fractures have been reported in patients treated with bisphosphonates. Their incidence has been determined from registered data analysis using international codes. Therefore, the aim of our study was to estimate the real frequency of typical and atypical sub-trochanteric or diaphyseal fractures, based on radiological and clinical data compared to registered data. METHODS: In the registers of three large French University Hospitals, patients identified with International Classification of Diseases, 10th Revision diagnosis codes for sub-trochanteric or diaphyseal fracture were selected. Frequencies of ordinary and atypical fractures were calculated after both registered data, radiological and clinical files analysis. RESULTS: Among the 4592 patients hospitalized for a femoral fracture over 5 years, 574 were identified to have had a sub-trochanteric or femoral shaft fracture. 47.7% of the sub-trochanteric and femoral shaft fractures were misclassified, predominantly in the sub-trochanteric fractures subset. 12 patients had an atypical fracture (4% of the sub-trochanteric and femoral shaft fractures) and 11 fractures presented radiological features of atypical fractures, whereas clinical files analysis revealed they were pathological or traumatic fractures. CONCLUSION: Atypical fractures frequency is very low. Because of their low frequency and the unreliability of registered databases, the risk of atypical fractures is very difficult to estimate retrospectively. A prospective study is needed to clarify the risk factors associated with these fractures.

Prognostic interest of bone turnover markers in the management of postmenopausal osteoporosis.

OBJECTIVE: The aim was to review the literature dealing with the use of biochemical bone turnover markers (BTM) as predictors of bone loss and individual risk of fracture in postmenopausal osteoporosis. METHODS: We performed a generalized search in MEDLINE using Mesh Database from 1995 through 2009 with the following terms "biological markers" with "osteoporosis" or "bone resorption", or "bone fracture", "fracture risk". From this research, 197 abstracts were read, 91 articles were screened then 43 original articles were selected. RESULTS: In most of the selected articles, the upper limit of the premenopausal range was used as a cut-off definition for increased bone resorption. Based on this review, we found a moderate and positive relationship between baseline level of BTM and rate of bone loss, more particularly for high level of BTM over 2 SD, especially when high turnover is constant in repeated sampling. In addition, an increase in BTM levels is associated with an increase in the risk of hip and non-vertebral fractures in elderly women over 75 years old. This is especially demonstrated with bone resorption markers (e.g. uCTX) in the highest quartile with an 1.7 to 2.2 fold increase. The combination of data from bone mineral density (BMD) and bone resorption markers may improve fracture prediction. CONCLUSION: The measurement of BTM, together with the assessment of other risk factors including low BMD, will improve the prediction of risk fracture, but there is a lack of practical guidelines.

Bone turnover markers for osteoporotic status assessment? A systematic review of their diagnosis value at baseline in osteoporosis.

OBJECTIVE: Osteoporosis diagnosis is based on bone mineral density (BMD) but bone remodeling is also a crucial issue. It can be assessed by bone turnover markers (BTMs). Their interest for the positive and etiological diagnosis of osteoporosis at baseline, and their predictive value for past asymptomatic vertebral fractures, were evaluated by a systematic review of the literature. METHODS: Medline database was searched to identify all published reports analyzing BTMs and BMD or fractures. We conducted meta-analyses on BTMs levels according to osteoporotic status using random effects models. RESULTS: Moderate and negative correlations were found, mainly in postmenopausal women, between BTMs and BMD, especially with bone alkaline phosphatase (bone ALP), osteocalcin, serum C-terminal and urine N-terminal crosslinking telopeptides of type I collagen (sCTX and uNTX). Bone ALP and sCTX levels are higher in osteoporotic patients compared to controls. High levels of bone ALP in primary hyperparathyroidism and low levels of osteocalcin in endogenous hypercorticism are the most relevant data reported in endocrine diseases associated with osteoporosis. High levels of BTMs, especially osteocalcin, bone ALP or sCTX, may be associated with prevalent vertebral fractures. CONCLUSION: The diagnosis value of BTMs at baseline in osteoporosis is very low. The interest of BTMs for the etiological diagnostic of secondary osteoporosis has not been demonstrated. Data are lacking to address the interest of BTMs assessment to screen for vertebral fractures in asymptomatic patients with high risk factors of fractures.

Functional hypoparathyroidism in postmenopausal women with fragility fracture.

INTRODUCTION: Secondary hyperparathyroidism sometimes is lacking despite authentic vitamin D insufficiency (VDI) and the concept of functional hypoparathyroidism with a protective role on bone status has been proposed. Therefore, we tested the hypothesis that its prevalence was very low in a population of women with a peripheral fragility fracture. METHODS: We conducted our study in postmenopausal women, admitted for such a fracture in our Fracture Liaison Service. All had bone mineral density (BMD), biochemical assessment and a medical visit. RESULTS: Two hundred and thirty seven women (72.9±11.6-year-old) were included and 90.4% had VDI (25[OH]D≤30 ng/mL). Yet, 87.9% of the latter had normal PTH levels less or equal to 64 ng/L. In this population with VDI (n=214), we found no PTH plateau level related to 25(OH)D. Since a recent study reported an increase in the risk of fracture only when 25(OH)D was below 15 ng/mL, we then used this value as a new threshold. We observed a significant difference in hip BMD between patients with 25(OH)D either less or equal to or greater than 15 ng/mL. However, 81.2% of the formers were still with normal PTH with no difference in BMD whether PTH level was above or within normal range. CONCLUSION: In a population of postmenopausal women with a fragility fracture, we found that 25(OH)D less or equal to 15 ng/mL was associated with significantly lower hip BMD. Even using this low threshold, we found a high prevalence of functional hypoparathyroidism and it was not associated with any difference in hip or spine BMD. Overall, our results do not support the hypothesis of a protective effect of this biological profile.

Clinical utility of serum bone turnover markers in postmenopausal osteoporosis therapy monitoring: a systematic review.

OBJECTIVES: Serum bone turnover markers (sBTM) are used in clinical practice for patients undergoing postmenopausal osteoporosis therapy. The aim of this study was to systematically analyze the literature on the ability of sBTM to monitor therapy, focusing on the following 5 objectives: (1) pretreatment values and treatment choice; (2) short-term changes and clinical response; (3) sBTM effect on persistence to therapy; (4) sBTM ability to predict fracture risk after withdrawal of therapy; and (5) the prediction of serious adverse effects. METHODS: A systematic search on Medline completed manually was performed until November 2010 and was limited to postmenopausal osteoporosis and marketed therapies. RESULTS: Following the PRISMA statement for systematic reviews, 48 studies were selected. Baseline sBTM levels were not able to predict fracture risk reduction with either treatment. There was more evidence for the prediction of fracture risk reduction with bone formation sBTM including PINP than with sCTX. Most of the studies found correlations between sBTM and bone mineral density (BMD) changes under antiresorptive therapies, although inconsistently. The only published study on the impact of sBTM on persistence to therapy showed negative results. There was no evidence that sBTM allow the prediction of adverse effects, especially osteonecrosis of the jaw. CONCLUSIONS: sBTM reflect the skeletal effects of anti-osteoporotic treatments. Pretreatment values are not recommended for selecting therapy. Short-term changes are significantly correlated with BMD variation, but there is no published evidence that they predict benefit on fracture risk at the individual level.

Longitudinal myelitis in a patient with systemic lupus erythematosus.

Longitudinal myelitis is an exceedingly rare complication of systemic lupus erythematosus (SLE), of which only 11 cases have been published so far. We report a case in a 65-year-old woman in whom spinal cord dysfunction developed over several weeks, resulting in tetraparesis. She had a known history of SLE with a circulating anticoagulant. Magnetic resonance imaging of the spine and a stereotactic biopsy of a brain lesion established the diagnosis of SLE-related longitudinal myelitis. High-dose glucocorticoid therapy had started to bring about an improvement when she experienced a series of complications that were eventually fatal. Her case is unusual in that longitudinal myelitis is exceedingly rare in patients with SLE.