The Trabecular Bone Score Predicts Spine Fragility Fractures in Postmenopausal Caucasian Women Without Osteoporosis Independently of Bone Mineral Density.

INTRODUCTION: The trabecular bone score (TBS) is a gray-level textural metric that can be extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry (DXA) image. TBS is related to bone microarchitecture. Several literature data suggest that TBS predicts fracture risk as well as lumbar spine bone mineral density (LS-BMD) measurements in postmenopausal women. OBJECTIVE: A retrospective case-control study assessing the ability of the TBS to predict spine fragility fractures (SFF) in postmenopausal women with or without osteoporosis (diagnosed by T-score≤-2.5). METHODS: LS-BMD and the TBS were determined in the L1-L4 vertebrae. Statistical analyses were carried out in the entire group of women (entire-group) (n.699), in women both with osteoporosis (osteoporosis-subgroup) (n.253) and those without osteoporosis (non-osteoporosis-subgroup) (n. 446). RESULTS: At the unpaired t-test, both the TBS and the LS-BMD (p≤0.001) were lower in women with SFF (n.62) in the entire-group. In the non-osteoporosis subgroup, the TBS (p≤0.009) was lower in women with SFF (n.29). In the osteoporosis subgroup, the LS-BMD (p≤0.003) was lower in women with SFF (n.33). Considering the TBS and LS-BMD separately in a block logistic regression, the TBS was associated with SFF in the entire-group (odds ratio (OR): 1.599, 95% confidence interval (CI): 1.021-2.128) and in the non-osteoporosis-subgroup (OR: 1.725, 95% CI:1.118-2.660) whereas LS-BMD was associated with SFF in the entire-group (OR: 1.611, 95% CI: 1.187-2.187) and in the osteoporosis-subgroup (OR: 2.383, 95% CI: 1.135-5.003). According to forward logistic regression, entering the TBS, LS-BMD and confounders as predictors, the LS-BMD in the entire-group (OR: 1.620, 95% CI: 1.229-2.135) and in the osteoporosis subgroup (OR: 2.344, 95% CI: 1.194-4.600), and the TBS in the non-osteoporosis subgroup (OR: 1.685, 95% CI: 1.131-2.511) were the only predictors of SFFs. CONCLUSIONS: In the entire-group, the TBS predicted SFFs almost as well as LS-BMD, but not independently of it. The TBS, but not LS-BMD, predicted SFFs in the non-osteoporosis subgroup.

Osteobiography of a 19th century elderly woman with pertrochanteric fracture and osteoporosis: a multidisciplinary approach.

In this paper the osteobiography of an elderly woman recovered from a cemetery tomb where she was buried in 1850, affected by hip fracture and osteoporosis, is described. The overall anthropological characteristics of the individual have been investigated. Macroscopic, radiographic, tomographic, microscopic, and chemical and structural examinations have been performed to give a detailed account of the condition of the skeleton. A non-union pertrochanteric fracture not surgically treated and probably due to senile osteoporosis was diagnosed. The consequences of the fracture to the bones show that this individual likely survived several years following the injury. The osseous features we describe (remodelled bone at the fracture site, asymmetry of entheseal changes likely related to the particular walking pattern of the individual) may be useful in personal identification of skeletons of legal interest. Regarding the recognition of osteoporosis in unearthed skeletons, our study underlines that the cortical thickness, microscopic features, degree of crystallinity and Ca/P ratio represent more useful elements than the mean bone density, mineral/matrix ratio and mineral maturity, which are more sensitive to diagenetic changes that affect the mineral phase post-mortem.

Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up.

INTRODUCTION: Corticosteroid treatment is the standard of care in Duchenne muscular dystrophy (DMD), but the optimal age to initiate treatment and dosage pattern remain a matter of discussion. METHODS: We performed a long-term study of alternate-day corticosteroids in five 2- to 4-year-old DMD patients. The primary outcome measure was prolongation of the ability to walk. RESULTS: One patient lost ambulation at age 10. Four patients, aged 16 to 18 were fully ambulant, and 3 of them could still climb stairs. Respiratory function was moderately reduced in 2. Left ventricular ejection fraction was > 45%. Short stature and delayed puberty were the most relevant side effects. Although the negative impact of corticosteroid treatment on growth rate remained their major concern, parents and patients stated that they preferred corticosteroid therapy. CONCLUSIONS: Long-term corticosteroid treatment is effective in prolonging function but not in recovering lost function, and its early use seems appropriate.

Cyclosporine A in Ullrich congenital muscular dystrophy: long-term results.

Six individuals with Ullrich congenital muscular dystrophy (UCMD) and mutations in the genes-encoding collagen VI, aging 5-9, received 3-5 mg/kg of cyclosporine A (CsA) daily for 1 to 3.2 years. The primary outcome measure was the muscle strength evaluated with a myometer and expressed as megalimbs. The megalimbs score showed significant improvement (P = 0.01) in 5 of the 6 patients. Motor function did not change. Respiratory function deteriorated in all. CsA treatment corrected mitochondrial dysfunction, increased muscle regeneration, and decreased the number of apoptotic nuclei. Results from this study demonstrate that long-term treatment with CsA ameliorates performance in the limbs, but not in the respiratory muscles of UCMD patients, and that it is well tolerated. These results suggest considering a trial of CsA or nonimmunosuppressive cyclosporins, that retains the PTP-desensitizing properties of CsA, as early as possible in UCMD patients when diaphragm is less compromised.

Osteosynthetic improvement of osteoporotic bone: prevention surgery.

A prior osteoporotic femoral neck fracture (FNF) doubles the risk of a second, contralateral hip fracture. Pharmacological prevention of osteoporotic fractures is cost-effective but medication compliance and persistence rates are suboptimal.The aim of our study was to evaluate the safety and effectiveness of a device developed for the surgical prevention of an additional contralateral FNF in elderly osteoporotic patients.Only patients with a T score ≤ -2.5 were enrolled and randomized either to receive (Group A) or not receive (Group B) surgical prevention. Sixty-seven patients were enrolled. The mean follow-up was 16 months (range 1 to 22). To date, no contralateral FNF has been reported in either group. In Group A, no device-related complications were recorded. Twelve patients reported one or more falls and in four cases a non-femoral fragility fracture occurred.The main problem with pharmacological prevention is therapy adherence and the extensive period needed for only a slight improvement in bone strength.Surgical prevention is a potential solution for avoiding the occurrence of a second contralateral FNF. Nevertheless, a longer follow-up and a larger cohort of patients is necessary in order to verify the true effectiveness of the surgical prevention in elderly osteoporotic patients.

Effects of pulsed electromagnetic stimulation on patients undergoing hip revision prostheses: a randomized prospective double-blind study.

In this prospective, randomized, double-blind study, the effect of Pulsed Electromagnetic Fields (PEMFs) was investigated in 30 subjects undergoing hip revision using the Wagner SL stem. The subjects were treated for 6 h/day up to 90 days after revision. Study end points were assessed clinically by the functional scale of Merle D'Aubigné and instrumentally by Dual-Energy X-ray Absorptiometry (DXA) at the Gruen zones. Subject improvement according to Merle D'Aubigné scale was higher (P < 0.05) in subjects undergoing active stimulation compared to placebo. In analyzing the DXA findings, we subtracted for each area the postoperative bone mineral density (BMD) values from those measured at 90 days and we considered all results above 3.5% as responders. There were no significant differences in the average BMD values at each Gruen zone between the two groups both postoperatively and at 90 days investigation. In Gruen zones 5 and 6, corresponding to the medial cortex, we observed six responders (40%) in both areas in the control group, while in the stimulated group we observed 14 (93%) and 10 (66%) responders, respectively (both P < 0.05). This study showed that PEMF treatment aids clinical recovery and bone stock restoration.

Relationship of body mass index with main limb fragility fractures in postmenopausal women.

Body mass index (BMI) has been found to be related to the risk of osteoporotic hip fractures in women, regardless of bone mineral density (BMD). The same relationship is under debate for other limb fragility fractures. Very few studies have investigated the comparison of fracture risk among BMI categories, classified according to the WHO criteria, despite the potential usefulness of such information for clinical purposes. To address these issues we studied 2,235 postmenopausal women including those with fragility fractures of the hip (187), ankle (108), wrist (226) and humerus (85). Statistical analyses were performed by logistic regression by treating the fracture status as the dependent variable and age, age at menopause, femoral neck BMD and BMI as covariates. BMI was tested as a continuous or categorical variable. As a continuous variable, increased BMI had a protective effect against hip fracture: OR 0.949 (95% CI, 0.900-0.999), but carried a higher risk of humerus fracture: OR 1.077 (95% CI, 1.017-1.141). Among the BMI categories, only leanness: OR 3.819 (95% CI, 2.035-7.168) and obesity: OR 3.481 (95% CI, 1.815-6.678) showed a significantly higher fracture risk for hip and humerus fractures, respectively. There was no relationship between ankle and wrist fractures and BMI. In conclusion, decreasing BMI increases the risk for hip fracture, whereas increasing BMI increases the risk for humerus fractures. Leanness-related low BMD and obesity-related body instability might explain the different BMI relationships with these two types of fracture.

Relationship of a lifelong physical workload with physical function and low back pain in retired women.

BACKGROUND AND AIMS: The effect of heavy work-related physical loads (WRPL) on low back pain (LBP) and impaired physical function has been studied extensively in active workers but not in pensioners. METHODS: We compared LBP and physical function in post-menopausal pensioners, divided according to their life-long WRPL into 114 heavy physical workers (HPW), and 391 light physical workers (LPW). LBP and physical function (domains of mobility, home routines) were scored by a questionnaire. Data on age, age at menopause, number of years in retirement, age at menarche, number of pregnancies, body mass index (BMI), femoral neck bone density, WRPL, years spent at work, and smoking were also collected. RESULTS: HPW were older (p=0.004), had worked fewer years (p=0.001), had reduced mobility (p=0.001), worse LBP (p=0.001) and performed home routine activities worse (p=0.001) than LPW. Logistic regression adjusted for confounders (LBP, home routines and mobility dichotomised at the median) showed that heavy WRPL, aging and high BMI were LBP risk factors, whereas heavy WRPL, high BMI and early menopause were mobility risk factors. The area under receiver-operating characteristic curves showed that predicted probabilities, derived from logistic models, predicted mobility (area 0.816, SE 0.020) better than pain (area 0.643, SE 0.024) (Hanley McNeil test p<0.001). CONCLUSIONS: Lifelong heavy WRPL and high BMI seem to be risk factors for worse LBP and mobility in retired women. Mobility seems to be especially affected by these risk factors, and should be further investigated for prevention purposes.

Relationship between body composition and bone mineral density in women with and without osteoporosis: relative contribution of lean and fat mass.

To assess the relationship of total fat mass (TFM) and total lean mass (TLM) with bone mineral density (BMD) and bone mineral content (BMC), we studied 770 postmenopausal white women after total body measurements by dual-energy X-ray absorptiometry. Height-independent bone mineral density (HIBMD) was also tested. The effects of TFM and TLM on the dependent variables HIBMD, BMD, and BMC were assessed by the univariate general linear model (UGLM). Age, age at menopause, height, and bone area were entered in the models as controlling variables when appropriate. In the total population, TLM and TFM were associated with BMD, BMC, and HIBMD (P < 0.001). Taking the T-score cut-off as -2.5, women without (463) and with (307) osteoporosis were then tested separately. In nonosteoporotic women, TLM was significantly associated with BMD, BMC, and HIBMD (P < 0.001), while TFM was not. In osteoporotic women, both TLM and TFM were associated with BMD to the same extent (P < 0.05), but not with HIBMD. Women without osteoporosis were then tested according to whether their TFM/TLM fraction was less than or greater than 1. In those with TFM/TLM less than 1, both TLM (P < 0.001) and TFM (P < 0.01), tested separately, were associated with BMD and BMC, but not with HIBMD. When TLM and TFM were tested at the same time and assessed by the same UGLM, only TLM (P < 0.001) still affected these three bone parameters. In women with TFM/TLM greater than 1, testing the body components both separately and at the same time and using the UGLM showed that TFM affected both BMC and BMD (P < 0.05), while TLM did not. In conclusion, our data indicate that both TFM and TLM affect bone density, with different physiological/pathological conditions modulating this relationship.

The relationship of vitamin D status to bone mineral density in an Italian population of postmenopausal women.

Several authors have found a relationship between vitamin D status and bone mineral density (BMD). To our knowledge, no previous studies on this topic have been carried out on the Italian postmenopausal population. We studied this relationship retrospectively in 156 Italian postmenopausal women. We also investigated the relationship between parathyroid hormone (PTH) and BMD. Measurements of BMD were taken at the lumbar spine and upper femur by dual X-ray absorptiometry. Serum 25(OH)D (calcidiol), 1,25(OH)2D (calcitriol), PTH, calcium, phosphorus, creatinine, osteocalcin and urinary calcium and phosphorus were measured according to the current laboratory methods of analysis. We found a positive statistically significant correlation between BMD, both at the spine and hip, and 25(OH)D, and a negative statistically significant correlation between BMD and PTH. No statistically significant correlation was found between BMD and 1,25(OH)2D. Crude logistic regression showed age, 25(OH)D and PTH were significant predictors of low BMD, while 1,25(OH)2D was not. Backward logistic regression showed 25(OH)D was the best predictive model for spine osteoporosis together with age, and on its own it was the best predictive model for femoral neck osteoporosis.

Clinical risk factor evaluation to defer postmenopausal women from bone mineral density measurement: an Italian study.

To identify clinical risk factors (CRFs) best related to low bone mineral density (BMD) and to assess their abilityin deferring women from dual-energy X-ray absorptiometry (DXA), 1187 Italian postmenopausal women, dividedinto development (709) and validation (478) groups, were studied. CRFs were investigated by questionnaire. DXAwas performed at the spine and femoral neck. A T-score < -2.5 at both measurement sites classified those with lowBMD. In the development group, using the logistic regression, the CRFs best predicting low BMD were years sincemenopause, age at menarche, weight, previous fracture, and muscle weakness. The predicted probability of low BMD(PPL-BMD), calculated by the logistic equation, was used to build receiver-operating characteristic (ROC) curves(area = 0.786, standard error [SE] = 0.017) on diagnosed BMD status. The PPL-BMD cutoff below which to deferwomen from DXA was set corresponding to the ROC curve sensitivity of 99%, 98%, and 97%. The coefficients ofthe logistic regression were then used to calculate the PPL-BMD of the validation group. In the validation group, theoverall ability of CRFs to predict low BMD (ROC area = 0.744, SE = 0.023) was not different from that of the developmentgroup. At the PPL-BMD cutoff of 0.132, the percentage of DXA-deferred cases (14.5% vs 19.0%) and low-BMD-missed cases (0.7% vs 1.7%) was similar in both groups. The rates of DXA-deferred women by CRFs arereproducible and this tool should be useful in clinical practice.

Quantitative ultrasound at the phalanxes discriminates osteoporotic women with vertebral but not with hip fracture.

Caucasian postmenopausal women with vertebral fracture (38), hip fracture (38) and without fracture (124) were measured by spine and femoral neck bone mineral density (BMD) (Norland XR 36), and two quantitative ultrasound (US) or QUS parameters (Igea DBM sonic 1200): the amplitude-dependent speed of sound (Ad-Sos) and the US bone profile score (UBPS), at the proximal hand phalanxes to investigate the ability of QUS to detect previous fracture. Age, height and weight were not different among groups, but menopausal age was lower with vertebral fracture (p < 0.005). QUS parameters of hip (AdSos = 1806.2 +/- 104.6 m s(-1); UBPS = 0.22 +/- 0.13) or spine fracture (AdSos = 1774.4 +/- 90.0 m s(-1); UBPS = 0.19 +/- 0.10) were not significantly lower than controls (AdSos = 1819.1 +/- 111.9 m s(-1); UBPS = 0.25 +/- 0.17), and BMD of hip (spine: 756.0 +/- 138.9 mg cm(-2); femoral neck: 583.6 +/- 61.8 mg cm(-2)) and vertebral (spine: 727.4 +/- 120.4 mg cm(-2); femoral neck: 592.8 +/- 82.1 mg cm(-2);) fracture was lower than controls (spine: 829.2 +/- 167.6 mg cm(-2); femoral neck 665.0 +/- 108.9 mg cm(-2)) (p < 0.001). Spine and femoral neck BMD significantly separated both types of fractures from controls, but AdSos and UBPS significantly separated only vertebral fractures. Femoral neck BMD has the best receiver operating characteristic (ROC) area for both hip (0.715, SE 0.043) and vertebral (0.693, SE 0.047) fractures, being significantly better (p < 0.01) than that of AdSos (0.503, SE 0.056) and UBPS (0.501, SE 0.057) for hip fractures, but not for vertebral fractures (AdSos 0.604, SE 0.050; UBPS 0.563, SE 0.048). In conclusion, QUS at hand phalanxes predicts vertebral fracture as effectively as BMD, but does not predict hip fracture.

Comparison between T-score-based diagnosis of osteoporosis and specific skeletal site measurements: prognostic value for predicting fracture risk.

T-score-based diagnosis of osteoporosis might lead to diagnostic misclassification when using multiple-site bone mineral density (BMD) measurements. To compare the diagnostic concordance of T-score-based diagnosis of osteoporosis among different skeletal sites and its correlation to osteoporotic fracture, we studied 1200 postmenopausal women with (441) and without (759) fragility fracture after measuring BMD at the femoral neck, Ward's triangle, trochanter, and spine. Agreement rates of T-score-based diagnosis of osteoporosis were statistically different between pairs of measurements taken at different skeletal sites (McNemar test, p < 0.001). Fragility fractures poorly matched T-score-based diagnosis of osteoporosis (Cohen and Younden indexes <0.4). Technique inaccuracies support these discrepancies as also shown by the large range of T-score values (from -2 to -3) with similar abilities to predict fractures by ROC curve area comparison. Concordance rates between T-score and fragility fracture diagnosis of osteoporosis (marginal homogeneity test, p < 0.001) were also different across the various measurement sites. Our data show that the T-score leads to diagnostic inconsistencies among different skeletal sites and low concordance with fragility fracture based diagnosis of osteoporosis. Integration of the T-score with multiple risk assessment from clinical sources should be tested to better diagnose osteoporosis and related fracture risk.

Early prednisone treatment in Duchenne muscular dystrophy.

The purpose of this long-term, open parallel-group, double-consent study of alternate-day, low-dose prednisone in 2-4-year-old patients with Duchenne muscular dystrophy (DMD) was to determine whether prednisone produces a beneficial effect when given earlier than usual. Muscle function was evaluated by timed tests, and muscle strength with a hand-held myometer. After 55 months of treatment, the five patients (mean age 8.3 years) in the prednisone group were still able to get up from the floor, whereas two of the three in the control group had lost this ability. Side effects included a decline in growth rate in the prednisone-treated patients and excessive weight gain in one control and three treated patients. Because steroids are effective in prolonging function, but not in recovering lost function, we propose that treatment be started with low-dose prednisone in DMD patients as soon as the diagnosis is definite.

Prediction of hip fracture can be significantly improved by a single biomedical indicator.

Femoral neck fractures are a relevant clinical and social problem. The aim of this study was to improve the prediction of patients at-risk of femoral neck fracture with respect to the current densitometric-based methods. In particular, finite element models were used to assess the prediction accuracy obtained by combining together data from the bone density distribution, the proximal femur anatomy, and the fall-related loading conditions. Two-dimensional finite element models were developed based on dual energy x-ray absorptiometry data. A population of 93 elder Caucasian women (half of them reporting a femoral neck fracture) were retrospectively classified both using the standard clinical protocol and Bayes' linear classifiers. This study showed that the bone mineral density in the femoral neck region dominated the fracture event (65% accuracy). Adding the subject's height and the neck-shaft angle to the bone density increased the accuracy to 77%. The classification accuracy was further improved to 82% by including the peak principal tensile strain obtained from the finite element analyses. This research demonstrated that adding one single biomechanical indicator to the standard clinical measurements improves the identification of patients at-risk of femoral neck fracture.