The French multicentre elevated bone mass study: prevalence and causes.

The purpose of this multicentric study was to evaluate the prevalence and causes of Elevated Bone Mass (EBM) in patients who underwent DXA scanning over a 10-year period. The prevalence of EBM was 1 in 100. The main causes of EBM were degenerative spine disorders and renal osteodystrophy. INTRODUCTION: Reports of elevated bone mass (EBM) on routine dual energy X-Ray absorptiometry (DXA) scanning are not infrequent. However, epidemiological studies of EBM are few and definition thresholds are variable. The purpose of this French multicentric study was to evaluate the prevalence and causes of EBM in adult patients who underwent DXA scanning over a 10-year period. METHODS: This multicentric, retrospective study was conducted in six French regional bone centres. DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥ +4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. RESULTS: In all, 72,225 patients with at least one DXA scan were identified. Of these, 909 (322 men and 587 women) had a Z-score ≥ + 4, i.e. a prevalence of 1.26% [1.18-1.34%]. The DXA scan reports and imagery and medical records of the 909 EBM patients were reviewed and 936 causes were found. In 42 patients (4%), no cause could be determined due to unavailability of data. Artefactual causes of EBM were found in 752 patients (80%), in whom the predominant cause was degenerative disease of the spine (613 patients, 65%). Acquired causes of focal EBM-including Paget's disease (n = 7)-were found in 12 patients (1%), and acquired causes of generalized EBM-including renal osteodystrophy (n = 32), haematological disorders (n = 20) and hypoparathyroidism (n = 15)-in 84 patients (9%). Other causes were rare hereditary diseases and unknown EBM in 19 (2%) and 27 (3%) cases respectively. CONCLUSIONS: The prevalence of EBM was approximately 1 in 100. These findings suggest that degenerative disease of the spine is the main cause of EBM, but that acquired or hereditary diseases are also causal factors.

DXA-based variables and osteoporotic fractures in Lebanese postmenopausal women.

INTRODUCTION: The aim of this study was to assess DXA-based variables (bone mineral density, bone mineral apparent density, compressive strength index of the femoral neck and trabecular bone score) in Lebanese postmenopausal women having presented a previous fracture. MATERIALS AND METHODS: One thousand Lebanese postmenopausal women between 45 and 89 years participated in this study. The women were recruited by advertisements offering bone mineral density measurements at a reduced cost. Subjects with previous history of radiotherapy or chemotherapy were excluded. Informed written consent was obtained from all the participants. RESULTS: Femoral neck compressive strength index (FN CSI) was significantly (P<0.001) associated with the presence of fracture using a simple logistic regression (odds ratio=0.51 [0.385-0.653]). When a multivariate logistic regression analysis was performed with the presence of fracture as a dependent variable and each of age, FN BMD and FN CSI as independent variables, only FN BMD (P=0.005) and FN CSI (P=0.004) were found to be associated with the presence of fracture. CONCLUSION: This study suggests that FN CSI is associated with history of osteoporotic fractures in postmenopausal women. The use of FN CSI in clinical practice may help to identify patients with high risk of fracture. LEVEL OF EVIDENCE: Epidemiological study, level IV.

Predictive factors of change in BMD at 1 and 2 years in women with anorexia nervosa: a study of 146 cases.

UNLABELLED: Bone mineral density (BMD; measured by DXA) changes were observed at all sites at 1 year in 146 patients with anorexia nervosa. Four independent factors accounted for the variation in BMD at the spine: duration of anorexia, bone-specific alkaline phosphatase (BAP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and triiodothyronine (T3). No change in BMD was observed from 1 to 2 years during follow-up. INTRODUCTION: The purpose of this study was to assess changes in BMD at 1 and 2 years in anorexia nervosa patients, and to explore the relationships between change in BMD and various clinical and biological parameters measured at the first visit. METHODS: BMD was measured in anorexia nervosa patients at inclusion, at 1-year follow-up (n = 146) and at 2-year follow-up (n = 89). RESULTS: Bone loss was observed at all sites at 1 year. When multivariate analyses were performed, four independent factors accounted for the variation in BMD at the spine: duration of anorexia nervosa, BAP, ICTP, and T3. At the total hip site, leptin level was the main factor accounting for the variation in BMD. Strong correlations were also observed between weight at 1 year and change in BMD at 2 years. At the 2-year follow-up, no significant change in BMD was observed at the spine or femoral neck. In patients who were no longer amenorrheic at 1 year, a significant improvement in BMD at 2 years was observed at the total hip (+1.2%, p = 0.02) and femoral neck (+3.7%, p = 0.02). Similarly, in patients with a body mass index >17 kg/m(2) at 1 year, an improvement in BMD at the total hip at 2 years was observed (+3%, p = 0.02) CONCLUSION: Bone loss in anorexia nervosa patients occurs at an early stage, and the factors influencing such are different at the spine and hip.

Anorexia nervosa, osteoporosis and circulating leptin: the missing link.

UNLABELLED: Methods: Leptin levels were measured in 103 consecutive women with anorexia nervosa. Results: Spine BMD and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. INTRODUCTION: The purpose of this study was to assess leptin levels and other biological variables in a population of anorexia nervosa patients. METHODS: Leptin levels were measured consecutively in 103 women with anorexia nervosa (AN) with a mean age of 24.9 +/- 7.4 years. Osteodensitometry was also performed by dual energy X-ray absorptiometry (DXA). RESULTS: Spine bone mineral density (BMD) and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. The mean leptin level was 3.9 +/- 4.6 ng/mL (normal values, 3.5-11 ng/mL). The distribution of leptin values was not a Gaussian distribution, and a log-transformed was therefore performed. A significant correlation was found between leptin level and spinal BMD (r = 0.3; p = 0.002); significant correlations were observed for both femoral neck and total hip BMDs. When leptin level values were divided into tertiles, spine BMD and Z-score values were found to be significantly lower in the lower tertile (p = 0.04 and p = 0.02) compared with the highest tertile. For femoral neck BMDs, the T-score was slightly lower between low and high tertile, but the difference was not statistically significant (p = 0.07). When multivariate analyses were performed, two independent factors which could possibly account for the variance in spinal BMDs were found. Duration of amenorrhea and leptin level accounted for 27% of the variance (p < 0.0001). CONCLUSION: The mechanisms underlying bone loss in AN patients remain unclear and complex, involving hypoestrogenia as well as nutritional factors such as insulin-like growth factor and leptin.

The usefulness of bone remodelling markers in predicting the efficacy of pamidronate treatment in SAPHO syndrome.

OBJECTIVES: Pamidronate has recently been used in SAPHO syndrome due to its anti-osteoclastic effect. The aim of this study is to determine the usefulness of bone remodelling markers for determining the efficacy of pamidronate treatment. METHODS: Thirteen patients with SAPHO syndrome were treated with pamidronate. The treatment evaluation was done using a visual analogue scale (VAS) and also erythrocyte sedimentation rate, C-reactive protein, serum crosslaps (sCTX) and osteocalcin initially and after 3 months. A relevant clinical response was defined as an improvement in VAS of at least 40%. RESULTS: At 3 months, 7 of 13 patients had a good clinical response, as previously defined. Five of the seven patients maintained the good response over 6 months. Before the first perfusion 6 of the 13 patients had increased sCTX (upper 3250 pmol/l). In this small cohort we tried to analyse whether the increase in bone remodelling markers was associated with a good clinical response. In the responders group the mean levels of sCTX and osteocalcin at baseline were 6783.17 and 24.66, respectively, and in the non-responders group the levels were 2152 and 11.8, respectively. There was a significant difference in sCTX between the responders and the non-responders (P = 0.0044). CONCLUSION: Infusion of pamidronate is effective in SAPHO in some patients. Increased sCTX might be a prognostic marker for a good clinical response but results have to be confirmed in a larger cohort.

Normal anatomy of the heel entheses: anatomical and ultrasonographic study of their blood supply.

The purpose of this study was first to determine the normal blood supply of the heel entheses with cadaver injection, and second, to identify by means of ultrasound (US) this blood supply in healthy volunteers before and after the intravenous injection of a US contrast agent (SonoVue). Twenty cadaver lower limbs were cut into sagittal, coronal, or axial sections after the injection of a red-colored gelatin solution. Ten anatomical samples were selected for histology. Then 10 healthy volunteers were enrolled in a contrast-enhanced ultrasonography study (CUS). Calcaneal tendon and plantar aponeurosis entheses were studied first without any contrast-agent (B-mode, power Doppler). A single dose (2.4 ml) of the contrast agent was then administered for studying each enthesis of the right foot. The operators had to look for blood flow within the entheses and in the adjacent soft tissues. Anastomotic transverse branches were seen macroscopically at the back of the calcaneal tendon, giving some capillaries penetrating the enthesis. None of these vessels could be seen with CUS. In contrast, a high-density vascular network could be detected in Kager's triangle with CUS. No blood vessel could be seen within the plantar aponeurosis enthesis, either macroscopically or microscopically. No evidence of entheseal vascularization was found with any contrast-enhanced imaging technique. Inferior branches of the lateral plantar artery were seen on coronal and sagittal sections of the hindfoot, and could be detected with CUS. These arterioles were running toward the anterior aspect of the calcaneal tuberosity, near the plantar aponeurosis insertion. In conclusion, no vascularization was detected with CUS at the cortical bone insertion of normal heel entheses. However, some vascularization could be seen in the immediate vicinity of heel entheses. The latter feature has to be kept in mind, as it may represent a pitfall for the diagnosis of early inflammatory changes in patients, especially those with seronegative spondylarthropathies.

Does quantitative ultrasound of bone reflect more bone mineral density than bone microarchitecture?

Relationships among quantitative ultrasound of bone (QUS), bone mineral density (BMD) and bone microarchitecture have been poorly investigated in human calcaneus.Twenty-four specimens, from 12 men and 12 women (mean age 78 +/- 10 years; range 53-93), removed from cadavers were studied. The feet were axially sectioned above the ankle. Two variables were measured for QUS (Achilles, Lunar): broadband ultrasound attenuation (BUA) and speed of sound (SOS). A third variable, the stiffness index (SI), which is a combination of both BUA and SOS, was also calculated. BMD (a lateral view) was measured on a QDR 2000 densitometer (Hologic). Bone microarchitecture was assessed by computed tomography (CT) using a conventional CT-system. Fifteen sagittal sections (1 mm in width and 2 mm apart) were selected for CT. Methods used for characterizing bone microarchitecture consisted in structural (trabecular network characterization) and a fractal analyses. The relationships between QUS and bone microarchitecture were assessed by simple linear regression analysis with and without adjustment for BMD (partial correlation) and by backward stepwise regression analysis. Strong relationships were found between BMD and QUS. Adjusted r(2) values were 0.545 for SOS and 0.717 for SI. Two microarchitectural variables were also significantly correlated with both SOS and SI: apparent trabecular separation (App Tr Sp) and trabecular bone pattern factor (App TBPF). After adjustment for BMD few correlations between QUS and microarchitectural variables were always significant. Adjusted squared semipartial coefficients of correlation (rsp2) values between SOS and bone microarchitecture were 6%, 6.8%, 13.2% and 4.6% for App BV/TV, App Tr Sp, App TBPF and fractal dimension (FD), respectively. For SI, corresponding figures were 3.7%, 4.1%, 5.2% and 3.2%. Backward stepwise regression analysis using BMD and microarchitecture showed a slight increase of r(2) values that varied from 8.4% for SI to 17.8% for SOS, compared with BMD alone. The current study suggests that although BMD is a major determinant of acoustic properties of human calcaneus, significant density independent relationships with bone microarchitecture should also be taken into account.

Quantitative ultrasound of bone in male osteoporosis.

Quantitative ultrasound (QUS) measurement, a different approach to bone fragility assessment, has already been attempted in women with osteoporosis but rarely in men. In order to test its value and ability to identify osteoporotic men, a case-control prospective study was conducted using the Lunar Achilles, a device that measures attenuation and velocity parameters. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI), a composite parameter, were assessed through the heel of 66 osteoporotic patients, and compared with the results in 35 controls. Patients had sustained a low-trauma fracture and/or had a lumbar and/or femoral bone mineral density (BMD) more than 2.5 SD below the young male reference value. As expected, all QUS parameters were statistically lower in patients, as were the dual-energy X-ray absorptiometry (DXA) measurements at the hip and lumbar spine. The two methods were compared for their ability to predict the risk of osteoporotic fractures. The odds ratios (ORs), with their 95% confidence limits, for fractures per 1 SD decrease were significant, especially for SOS and SI (OR = 2.3 [1.4-3.6] and 2.1 [1.3-3.3] respectively) and to a lesser extent for BUA (1.6 [1.0-2.4]). Our study suggests that QUS is associated with a history of low-trauma fracture in men; sensitivity is, however, less than when results are compared with BMD measurements (OR = 2.8 [1.6-5.0] and 3.4 [1.6-7.0] for lumbar spine and hip, respectively). Prospective studies are required before QUS can be recommended for clinical use in male osteoporosis.

Causes of osteoporosis in males. A review of 160 cases.

BACKGROUND: The discovery of osteoporosis in a male requires a careful search for a cause. OBJECTIVE: To evaluate etiologic factors in male osteoporosis. PATIENTS AND METHODS: Males admitted to our department for osteoporosis were included if they had a nontrauma-related vertebral or peripheral fracture and/or a spinal or femoral neck bone mineral density value 2.5 standard deviations or more below the mean in young subjects. The study was retrospective from 1990 to 1995 and prospective from 1996 to 1997. During the prospective part of the study, each subject underwent a standardized battery of laboratory tests including renal tubular function parameters. Causes identified during these two periods were compared. RESULTS: Of the 160 patients included in the study, 28.1% had idiopathic osteoporosis, 22.5% had alcoholic osteoporosis, 19.4% had glucocorticoid-induced osteoporosis, 12.5% had osteoporosis due to moderate idiopathic proximal tubule dysfunction, and 8.8% had senile osteoporosis. The proportion of patients with idiopathic osteoporosis was 30% (23/76) during the retrospective part of the study and 26% (21/84) during the prospective part (nonsignificant difference). Moderate idiopathic proximal tubule dysfunction was found in 2.6% (2/76) and 21.4% (18/84) of patients during these two parts of the study, respectively, a difference ascribable to the routine determination of tubule function parameters during the second part of the study. CONCLUSION: An exhaustive search for a cause decreases the proportion of male osteoporosis cases that remain idiopathic. In our study, only 28% of cases were classified as idiopathic, a term that probably indicates involvement of multiple interrelated factors.