Hip fracture incidence and social deprivation: results from a French ecological study.

The association between socioeconomic status (SES) and hip fracture (HF) incidence was analyzed in France in 2008. In men and women, a decrease in HF incidence was observed as the social deprivation index increased. This result may be partly due to the protective effect of increasing body weight against HF. INTRODUCTION: Regional variations in hip fracture (HF) incidence exist worldwide. Reasons for these variations remain unknown. As regional variations have also been observed for socioeconomic status, we analyzed the association between socioeconomic deprivation (SED) and HF incidence in France in 2008. METHODS: From the French Hospital National Database, we selected all HF encoded as primary diagnosis in persons aged 30 years and over. The recently published French version of the European Deprivation Index (EDI) was used for SED analysis, and an EDI score was measured for the year 2007 in each French local municipality. The EDI score was categorized in quintiles. Poisson regression was performed to examine the association between HF incidence and EDI adjusted for age and sex. The population attributable fraction (PAF) was measured to calculate the proportion of excess cases of HF associated with social affluence. RESULTS: In 2008, 83,538 HF were reported in France of which 59,143 were included in this study. Among them, 44,401 fractures occurred in women (75%) and 14,742 in men (25%). In both men and women, there was a decrease in the HF incidence with increasing SED index. In Poisson regression, the interaction of age class and sex was significant (p < 0.0001) and the EDI in quintiles was significantly associated with the incidence of HF (p < 0.0001). A higher number of people living in affluent residential areas corresponded to a higher risk of HF. The risk of HF is 2.42 times higher for those living in the most affluent group compared to those living in the most underprivileged group. The value of the PAF was calculated at 27.1%. CONCLUSION: Social disparities in HF incidence exist in France with the most deprived municipalities having the lowest incidence. Prior knowledge demonstrates the strong relationships between body weight and HF risk as well as between body weight and the SED. The link found in our study between EDI and HF incidence as well as regional and temporal variations in HF incidence may be partly due to the protective effect of increased body weight against HF.

Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry.

OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.

Beneficial effects of vitamin D on falls and fractures: is cognition rather than bone or muscle behind these benefits?

The beneficial effect of vitamin D on bone tissue has long been attributed mainly to its positive effect on the intestinal absorption of calcium and on bone mineralization, which increases the bone mineral density (BMD) and thus decreases the risk of fracture. Recently, numerous extra osseous effects of vitamin D have been described, amongst them a positive effect on neuromuscular and cognitive functions. Several lines of evidence suggest that the beneficial effects of vitamin D on fall and fracture risk can be explained more by its action on the neuromuscular and cognitive functions than by its direct effect on bone metabolism. In this review, we first report on the relationships between vitamin D and osteoporotic fracture risk. Then, we present the data from the literature regarding the effects of vitamin D on risk factors such as fall risk and reduction in BMD, physical performance, and cognitive performance. Specific emphasis is put on the latter because there is evidence of a relationship between low concentration of serum 25-hydroxyvitamin D (the primary indicator of vitamin D status) and low cognitive abilities which have been shown to be a risk factor for falling. It can be further suggested that high risk of fracture in cognitively impaired adults could be explained by lower protective reaction when falling, which would result, for instance, from a lack of planning and foresight of the fall. Future studies are nonetheless needed to elucidate the associations between vitamin D and different risk factors, in particular the link between vitamin D and various cognitive functions.

Microbiological diagnosis of vertebral osteomyelitis: relevance of second percutaneous biopsy following initial negative biopsy and limited yield of post-biopsy blood cultures.

The purpose of this investigation was to evaluate the microbiological diagnosis yield of post-biopsy blood cultures (PBBCs) and second percutaneous needle biopsy (PNB) following an initial negative biopsy in vertebral osteomyelitis (VO) without bacteremia. A retrospective multicenter study was performed. Patients with VO, pre-biopsy negative blood culture(s), ≥1 PNB, and ≥1 PBBC (0-4 h) were included. One hundred and sixty-nine PNBs (136 first and 33 following initial negative biopsy) were performed for 136 patients (median age = 58 years, sex ratio M/F = 1.9). First and second PNBs had a similar yield: 43.4 % (59/136) versus 39.4 % (13/33), respectively. Only two PBBCs (1.1 %) led to a microbiological diagnosis. The strategy with positive first PNB and second PNB following an initial negative result led to microbiological diagnosis in 79.6 % (74/93) of cases versus 44.1 % (60/136) for the strategy with only one biopsy. In the multivariate analysis, young age (odds ratio, OR [95 % confidence interval (CI)] = 0.98 [0.97; 0.99] per 1 year increase, p = 0.02) and >1 sample (OR = 2.4 ([1.3; 4.4], p = 0.007)) were independently associated with positive PNB. To optimize microbiological diagnosis in vertebral osteomyelitis, performing a second PNB (after an initial negative biopsy) could lead to a microbiological diagnosis in nearly 80 % of patients. PBBC appears to be limited in microbiological diagnosis.

Denosumab use in bone fibrous dysplasia refractory to bisphosphonate: A retrospective multicentric study.

INTRODUCTION: Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates. MATERIALS AND METHODS: We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS). RESULTS: 13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good. DISCUSSION: This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS. CONCLUSION: Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.

Efficacy of rituximab in primary Sjogren's syndrome with peripheral nervous system involvement: results from the AIR registry.

OBJECTIVE: To evaluate rituximab (RTX) in primary Sjögren's syndrome (pSS) with peripheral nervous system (PNS) involvement. METHODS: Patients with pSS and PNS involvement who were included in the French AIR registry were analysed. RESULTS: 17 patients (age 60 years (44-78 years); 14 were female) were analysed. Neurological improvement was noted in 11 patients (65%) at 3 months. Rankin scale decreased from 3 (1-5) to 2 (1-5), 2 (1-5) and 2 (1-6) after 3, 6 and 9 months (p=0.02). European Sjögren's Syndrome Disease Activity Index decreased from 18 (10-44) to 11 (5-20), 11 (5-29) and 12 (5-30) after 3, 6 and 9 months (p<0.05). RTX was effective in neurological involvement in 9/10 patients with vasculitis or cryoglobulinaemia (90%) (group 1) at 3 months and in 2/7 cases (29%) without cryoglobulinaemia and vasculitis (p=0.03). Rankin and European Sjögren's Syndrome Disease Activity Index scales decreased significantly in group 1. CONCLUSION: RTX seems effective in cryoglobulinaemia or vasculitis-related PNS involvement in pSS.

Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the 'Orencia and Rheumatoid Arthritis' registry.

OBJECTIVES: Very limited data are available regarding the efficacy of abatacept (ABA) in real life. The aims of this study were to determine the efficacy of ABA in rheumatoid arthritis and predicting factors of efficacy in common practice. METHODS: The Orencia and Rheumatoid Arthritis" (ORA) prospective registry, promoted by the French Society of Rheumatology, has included 1003 patients with RA. RESULTS: 773 patients had already fulfilled the 6-month follow-up visit. Only 21.3% of patients would have fulfilled inclusion criteria used in pivotal controlled trials. The European League Against Rheumatism (EULAR) response, was observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%, moderate response: 38.7%) and was similar in patients who did and in patients who did not fulfill inclusion criteria of controlled trials. Among EULAR responders, initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0-6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs 66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In multivariate analysis adjusted on initial 28-joint disease activity score and CRP, anti-CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to 2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti-CCP positivity was also significantly associated with a higher ABA retention rate at 6 months. CONCLUSIONS: Real life efficacy of ABA in the ORA registry was similar as that reported in clinical trials. Anti-CCP positivity was associated with a better response to ABA, independently from disease activity.

A crystallinity study of dental tissues and tartar by infrared spectroscopy.

In this paper we report a study of an important property of biomineralized phases, crystallinity, on the basis of previous results for synthetic apatite. Crystallinity is not only important for understanding biomineralization, it is also related to the maturation and mechanisms of growth of calcium phosphates in biological surroundings. We studied two kinds of sample, teeth as an example of biomineralized tissues and dental calculi (adhering) as an example of mineralization without participation of biological agents, except possibly bacteria. The investigation focused on study of ν(1)-ν(3) infrared absorption bands of PO(4)(3-) phosphates. We used ATR (attenuated total reflection) analysis to examine human dental tissues and tartar on several samples. The results confirm for the first time previous assumptions about the growth and maturation of dental calculi, i.e., crystallinity progresses from regions of high crystallinity to regions of lower crystallinity, and, in addition, its quantification with spatial resolution in the sample. A gradual pattern was observed in dental calculus. Another result from this study was that cementum and dentine had similar crystallinity, despite their different biological and mechanical functions.

Inverse relationship between vertebral fractures and spine osteoarthritis in postmenopausal women with osteoporosis.

BACKGROUND: Although the coexistence of osteoarthritis and osteoporosis is considered as uncommon, it has been suggested that, in postmenopausal women, disc space narrowing increases the risk of vertebral fracture. The aim of this study was to check this hypothesis in postmenopausal women with osteoporosis. OBJECTIVE: We analysed the relationship between vertebral fractures and spine osteoarthritis in 410 postmenopausal women with osteoporosis: in this population both disc space narrowing and osteophytes are inversely related to vertebral fractures. PATIENTS AND METHODS: This study is based on baseline data collected in a multicentre, prospective and 6-month longitudinal observational study. 410 postmenopausal women (74+/-5 years) were enrolled who had consulted for back pain, and had osteoporosis (according to WHO definition). Spine x-rays were performed according to standardised procedures. Vertebral fractures were evaluated from T4 to L4 using the Genant's semiquantitative method; osteoarthritis was evaluated by scoring osteophytes and disc space narrowing at all levels of the thoracic and lumbar spine, and by a qualitative assessment of facet joint arthritis. RESULTS: The prevalence of vertebral fractures was 52.4%. At least one osteophyte, one disc space narrowing and one facet arthritis were present in 90.2, 64.6 and 77.8% of patients respectively. There was an inverse association between vertebral fractures and osteoarthritis: odds ratios adjusted for age and weight (95% CI) were 0.38 (0.17-0.86), p = 0.02 and 0.27 (0.16-0.46), p<10(-4) for the presence of at least one osteophyte, and of at least three disc space narrowings respectively. In a cluster analysis, it was possible to identify a subgroup of patients without any disc space narrowing, and another subgroup with all patients having at least one disc space narrowing; the proportion of patients having more than three vertebral fractures was 25.2 and 15.9% in these two clusters respectively. CONCLUSIONS: Disc space narrowing and osteophytes are associated with a decreased vertebral fracture prevalence in postmenopausal women with osteoporosis.

Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis.

OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other. CONCLUSIONS: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.

Recruitment of new osteoblasts and osteoclasts is the earliest critical event in the pathogenesis of human multiple myeloma.

Considering the special relation of human multiple myeloma (MM) to bones, it is of importance to clarify the early steps of bone involvement in this disease. In this work, using bone histomorphometry (including histoenzymologic and kinetic studies for the first time), we have evaluated the bone remodeling (i.e., bone resorption and bone formation rates) of 16 individuals with early MM in comparison with that of 10 with benign monoclonal gammopathy (BMG) and that of 17 patients with previously untreated overt MM. A significantly increased osteoblastic recruitment was observed in the individuals with early MM when compared with those with BMG (P less than 0.01). A significant (P less than 0.01) increased bone resorption (i.e., eroded surfaces, osteoclast numbers and surfaces) was observed from the early stage of MM in comparison with the BMG status where bone resorption remained within the normal range. At the tissue level, there was no difference in terms of bone resorption between early and overt MM. On the other hand, osteoblast activity was significantly reduced in patients with overt MM (P less than 0.05 by comparison with those with early MM). A significant enhancement of osteoblastic recruitment with an increased generation of new osteoclasts is an early critical event in the pathogenesis of human MM. Of particular importance is the early stimulation of osteoblasts, since these cells produce high amounts of IL-6, a potent myeloma cell growth factor and a critical cytokine for the formation of osteoclasts in the bone marrow.

Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome.

OBJECTIVE: To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). METHODS: A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. RESULTS: One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. CONCLUSION: In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.

Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease.

In order to clarify the mechanisms involved in the occurrence of lytic bone lesions (BL) in multiple myeloma (MM), we have compared the presenting myeloma-induced histological bone changes of 14 previously untreated MM patients with lytic BL with those of seven MM patients lacking lytic BL at presentation despite similar myeloma cell mass. A major unbalanced bone remodeling (increased bone resorption with normal to low bone formation) was the characteristic feature of patients presenting lytic BL. Furthermore, this unbalanced process was associated with a significant reduction of bone mass. Unexpectedly, a balanced bone remodeling (increase of both bone resorption and bone formation, without bone mass reduction) rather than a true lack of an excessive bone resorption was the usual feature of patients lacking lytic BL. Our current work clearly shows that a majority (72%) of patients with MM present an important unbalanced bone remodeling at diagnosis, leading to bone mass reduction and bone destruction (unbalanced MM). Some patients (20%) retain a balanced bone remodeling with initial absence of bone destruction (balanced MM). Few (8%) patients have pure osteoblastic MM without bone destruction.

In vivo effects of human recombinant transforming growth factor beta on bone turnover in normal mice.

Reports of the effects of TGF-beta on bone cells are conflicting and controversial. Different cell culture and organ culture models for both osteoblasts and osteoclasts have given different responses. In some the effects are dependent on prostaglandin synthesis, and in others they are prostaglandin independent. To determine the effects of TGF-beta on osteoblasts and osteoclasts in vivo and the role of prostaglandins in mediating these effects, we injected 2.5-5 micrograms TGF-beta into the subcutaneous tissue overlying the calvariae of normal mice for 2-5 days anc compared the morphologic responses in underlying calvarial bone with those in mice injected caused a marked increase in periosteal thickness (fivefold) and cellularity, morphologic changes in osteoblasts, and new mineralized bone formation. These effects were localized to the site of injection and were partially inhibited by concomitant indomethacin treatment. There was a parallel increase in osteoclast numbers in adjacent marrow spaces, and the osteoclasts formed were unusually large. In contrast, no increase in the numbers of osteoclasts was seen in indomethacin-treat animals. These data show that TGF-beta has powerful effects on local bone cell function in vivo and that these effects may be mediated, in part, by prostaglandin generation.

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.

Different morphometric and densitometric parameters predict cervical and trochanteric hip fracture: the EPIDOS Study.

We used an experimental software measuring the hip axis length (HAL) and bone mineral density (BMD) in specific regions of the lower and upper part of the femoral neck on dual-energy X-ray absorptiometry scans. To determine whether these parameters were significant predictors of the type of hip fracture, we measured 167 healthy women (controls), 24 women with trochanteric, and 42 women with cervical hip fractures within the EPIDOS prospective cohort. EPIDOS is a multicenter prospective study on risk factors for hip fracture performed in 7575 elderly women living at home, aged 75-95 and conducted in five French centers (Amiens, Lyon, Montpellier, Paris, Toulouse). Measurements were performed on data acquired at baseline before the occurrence of fracture. In the cervical fracture group, HAL was significantly longer than in controls (94.2 vs. 92.3, p = 0.03), and the associated odds ratio (OR) adjusted for age, weight, and total femoral neck BMD was significant (OR = 1.64, 95% confidence interval [CI] 1.06-2.55). In contrast, HAL was not significantly different from controls in the trochanteric fracture group. Femoral neck diameter was not a predictor of fracture. The upper and lower femoral neck BMD was lower in the trochanteric fracture group than in controls, and both measurements predicted trochanteric femoral neck fracture. In contrast, the prediction of cervical femoral neck fracture was enhanced by measuring only the upper part of the femoral neck (OR = 2.79 vs. 1.97 for the total femoral neck) while BMD of the lower part was not different from controls. Hip axis length is a predictor of femoral neck fracture. Femoral neck BMD distribution is different between cervical and trochanteric fractures. These results support the hypothesis of a different pathophysiological mechanism between the two types of hip fractures.

Expression of human transforming growth factor alpha by Chinese hamster ovarian tumors in nude mice causes hypercalcemia and increased osteoclastic bone resorption.

Transforming growth factor alpha (TGF-alpha) is a polypeptide regulator of cell growth produced by many malignant tumors. It stimulates osteoclastic resorption in bone organ culture and osteoclast-like cell formation in marrow culture. To determine whether tumor production of TGF-alpha can cause hypercalcemia in vivo, we used Chinese hamster ovarian (CHO) cells transfected with the human TGF-alpha gene (TCHO), which stably express and secrete TGF-alpha. We used nontransfected CHO cells as controls (CCHO). TCHO and CCHO were inoculated intramuscularly into one hindlimb of nude mice and grew as local solid tumors. After 4 weeks of TCHO tumor growth, plasma ionized calcium (Ca2+) increased to reach 1.48 +/- 0.03 mM (mean +/- SEM), whereas mice bearing similarly sized CCHO tumors and non-tumor-bearing mice (NTB) remained normocalcemic (normal range for Ca2+, 1.15-1.30 mM). Plasma TGF-alpha was undetectable by an ELIFA assay in all NTB mice, was markedly increased in all TCHO mice (5.75 +/- 0.78 ng/ml), and was slightly increased in CCHO mice (0.50 +/- 0.22 ng/ml). Quantitative bone histomorphometry showed a prominent increase in osteoclastic bone resorption in TCHO mice. These data suggest that TGF-alpha is a mediator of hypercalcemia and increased osteoclastic bone resorption in tumors that produce it in sufficient quantity.

Prevalence of vertebral fractures in French women older than 75 years from the EPIDOS study.

The aim of this study was to ascertain the prevalence and severity of vertebral fractures in French elderly women. We used spinal radiographs collected during the baseline examination of the Epidémiologie de l'Ostéoporose (EPIDOS) study, a multicentric prospective study of risk factors for hip fracture. A total of 7598 ambulatory women volunteers were recruited in the EPIDOS cohort using large population-based listings such as voter-registration lists. A subsample of 770 participants were selected for spinal radiographs using a systematic selection procedure. Anteroposterior and lateral radiographs of the thoracic and lumbar spine were reviewed by two trained rheumatologists using the semiquantitative (SQ) method described by Genant et al. [J. Bone Miner Res. 8 (1993) 1137]. Vertebral deformities that could be related to causes other than osteoporosis (i.e., Scheuermann's disease or osteoarthritis) were disregarded. The final analysis was made over 745 women after excluding 25 women whose spine radiographs were incomplete or of poor quality. The sample average age was 80.1 +/- 3.4 years. Vertebral fractures were found in 170 women: 22.8% (95% CI, 19.8-25.8%). A single, two, three, or more vertebral fractures were seen in 99 (58.2%), 43 (25.3%), and 28 (16.5%) of the 170 affected women, respectively. The prevalence of vertebral fractures increased with age from 19.0% (95% CI, 14.9-23.1%) among women 75-79 years old to 21.9% (95% CI, 17.3-26.5%) among those 80-84 years old and to 41.4%(95% CI, 31.0-51.7%) among those 85 years of age and over (Chi-square test for trend P < 0.00016). A significant correlation was found also between the number of vertebral fractures per woman and age (r = 0.108, P = 0.003) and between the spinal fracture index and age (r = 0.105, P = 0.004). We conclude that the prevalence of vertebral fractures is high in French ambulatory elderly women, which confirms the results of previous studies conducted in various Caucasian and Asian populations.

Adult lumbar scoliosis. Epidemiologic aspects in a low-back pain population.

The frequency and characteristics of definite lumbar scoliosis in an adult common low-back pain population (n = 671) were assessed by a clinical and radiologic prospective study. The prevalence was 7.5% (N = 50), increasing with age: 2% before 45 years; 15% after 60 years. Scoliosis was revealed by low-back pain in adulthood in 86% of the cases. The mean Cobb angle was 21 +/- 11.4 degrees. A Cobb angle of more than 30 degrees was noted in 16% of the scoliotics, thus 1% of the entire population. The proportion of women increased with the severity of the scoliosis. Right and left side scolioses were equally noted. A correlation between the Cobb angle and age was found (0.3 degrees/yr; P < 0.05). Rotatory olisthesis was noted in 34% of the cases, more often in right side curves (P < 0.01). The lumbar scoliotic patients were distinguished by a more advanced age (62 +/- 12.4 yr vs. 49.6 +/- 15.5 yr; P < 0.001), a greater proportion of women (72% vs. 48%; P < 0.01), and a more likely involvement of L3 and L4 radicular pain (P < 0.05). Radicular thigh pain was related to unstable curves (P < 0.01). The lumbar scoliotic patients thus constitute a subgroup within the low-back pain population.

Pagetic vertebral ankylosis and diffuse idiopathic skeletal hyperostosis.

STUDY DESIGN: A retrospective radiologic analysis of Paget's disease of the spine. OBJECTIVES: The prevalence, anatomic distribution, mechanisms of formation of Pagetic vertebral ankylosis (PVA) and the possibility of a relationship to diffuse idiopathic skeletal hyperostosis (DISH) were assessed in a large population of persons with Paget's disease. SUMMARY OF BACKGROUND DATA: Acquired vertebral ankylosis is not a common feature of the Paget's disease of the spine and its mechanisms of formation remain unknown. In some reports, PVA was associated with radiographic signs of DISH. METHODS: Of 337 Pagetic patients monitored in the Division of Rheumatology from 1961 to 1990, all 245 who had entire spine radiographs were selected for study. Radiographs were studied for signs of Pagetic vertebral lesions and for spinal lesions of DISH. RESULTS: The study group contained 156 men with a mean age of 68 years (range 37-92) and 89 women with a mean age of 71 years (range 50-89). Fourteen PVA were observed on the radiographs of 11 men (mean age 68 years; range 60-76). One PVA was cervical, eight were thoracic, one thoracolumbar, three lumbar, and one lumbosacral. Eighty of the two hundred forty-five patients (32.6%) had characteristic features of DISH. Eight out of the eleven patients with PVA also had evidence of spinal lesions of DISH and radiographic features of DISH were observed contiguous to ten of the fourteen PVA. CONCLUSIONS: The scarcity of PVA reported in the literature and in our study (4.4% of 245 patients) suggests that constant progression of the disease from one vertebra to another by invasion of intervertebral disc space is rare. However, the higher incidence of PVA in men, their preferential location at the thoracic spine and their association with lesions of DISH suggest that progression of Pagetic lesions by invasion of bridging osteophytes may be an important mechanism for the intervertebral spread of Paget's disease.