Deletion of Tfam in Prx1-Cre expressing limb mesenchyme results in spontaneous bone fractures.

INTRODUCTION: Osteoblasts require substantial amounts of energy to synthesize the bone matrix and coordinate skeleton mineralization. This study analyzed the effects of mitochondrial dysfunction on bone formation, nano-organization of collagen and apatite, and the resultant mechanical function in mouse limbs. MATERIALS AND METHODS: Limb mesenchyme-specific Tfam knockout (Tfamf/f;Prx1-Cre: Tfam-cKO) mice were analyzed morphologically and histologically, and gene expressions in the limb bones were assessed by in situ hybridization, qPCR, and RNA sequencing (RNA-seq). Moreover, we analyzed the mitochondrial function of osteoblasts in Tfam-cKO mice using mitochondrial membrane potential assay and transmission electron microscopy (TEM). We investigated the pathogenesis of spontaneous bone fractures using immunohistochemical analysis, TEM, birefringence analyzer, microbeam X-ray diffractometer and nanoindentation. RESULTS: Forelimbs in Tfam-cKO mice were significantly shortened from birth, and spontaneous fractures occurred after birth, resulting in severe limb deformities. Histological and RNA-seq analyses showed that bone hypoplasia with a decrease in matrix mineralization was apparent, and the expression of type I collagen and osteocalcin was decreased in osteoblasts of Tfam-cKO mice, although Runx2 expression was unchanged. Decreased type I collagen deposition and mineralization in the matrix of limb bones in Tfam-cKO mice were associated with marked mitochondrial dysfunction. Tfam-cKO mice bone showed a significantly lower Young's modulus and hardness due to poor apatite orientation which is resulted from decreased osteocalcin expression. CONCLUSION: Mice with limb mesenchyme-specific Tfam deletions exhibited spontaneous limb bone fractures, resulting in severe limb deformities. Bone fragility was caused by poor apatite orientation owing to impaired osteoblast differentiation and maturation.

Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure.

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure.

Significance of ß-catenin expression for the incidence of pathological fractures in giant cell tumors of bone.

Aim of the study is to determine the possible roles of p53, cyclin D1, ß-catenin and Ki-67 in the increase in risk of fractures in patients with giant cell tumor of bone. The study included a total of 164 patients with giant cell tumor of bone (GCTB), 21 (12.8%) with and 143 (87.2%) without fracture. The samples were analyzed immunohistochemically for expression of Ki-67, p53, cyclin D1 and ß-catenin. According to the immunohistochemical expression of p53 and Ki 67 in mononuclear stromal cells, as well as of cyclin D1 in multinuclear giant cells, there was no significant association with immunopositivity and risk of fractures. However, our research revealed that patients with cytoplasmic expression of b-catenin in stromal cells had three times more frequent occurrence of pathological fractures, which was highly statistically significant (χ2 = 7.065; p = 0.008). Moreover, a highly statistically significant correlation between the nuclear expression of ß-catenin in giant cells and the incidence of pathological fractures was also found (χ2 = 8.824; p = 0.003). The study showed that ß-catenin expression highly correlates with the incidence of pathological fractures in patients with GCTB. Taking into account that ß-catenin is closely linked to activation of the Wnt signaling pathway in GCTB pathogenesis, one could postulate that activation of the Wnt pathway is one of the contributing factors to locally destructive behavior of this tumor, as well as to the incidence of pathological fractures.

No genetic causal association between iron status and osteoporosis: A two-sample Mendelian randomization.

Objective: To explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR). Methods: Publicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR-Egger methods. The pleiotropy of MR results was determined using MR-Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results. Results: Based on IVW, MR-Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (Pbeta > 0.05 in all models). IVW and MR-Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (Pbeta> 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (Pbeta> 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (Pbeta>0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR. Conclusion: Our results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded.

Strontium ranelate decreases the incidence of new caudal vertebral fractures in a growing mouse model with spontaneous fractures by improving bone microarchitecture.

UNLABELLED: Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture. INTRODUCTION: The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures. METHODS: Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9 weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry. RESULTS: Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9 weeks of the study (-60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, -39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (-39%, -21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women. CONCLUSIONS: This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture.

Stimulative effects of Polygonum amplexicaule var. sinense on osteoblastic MC3T3-E1 cells.

CONTEXT: Polygonum amplexicaule D. Don var. sinense Forb. (Polygonaceae) (PAF) is a well known traditional herb used to treat some diseases, such as fractures, rheumatoid arthritis, muscle injury, and pain. However, its pharmacological mechanism of promoting the healing of fractures is still unknown. OBJECTIVE: The present study was designed to investigate the effects of PAF ethanol extracts on the proliferation and differentiation of osteoblastic MC3T3-E1 cell in vitro, thereby to illuminate the pharmacological mechanism to promote the healing of fractures. MATERIALS AND METHODS: The effects of PAF ethanol extracts on MC3T3-E1 cell proliferation and differentiation were detected by using CCK-8, cell cycle, alkaline phosphatase (ALP), and prostaglandin E(2) (PGE(2)) assays in vitro. RESULTS: The results showed that PAF ethanol extracts significantly stimulated cell proliferation at 0.1-100 µg/mL and the proportion of cells in S-phase increased from 16.33 to 27.29% in osteoblastic MC3T3-E1 cells. Moreover, PAF ethanol extracts increased ALP expression in MC3T3-E1 cells at the concentration from 0.1 to 100 µg/mL and inhibited PGE(2) production induced by TNF-α in osteoblasts at the concentrations ranging from 10 to 100 µg/mL in MC3T3-E1 osteoblasts. DISCUSSION AND CONCLUSION: These results indicated that PAF directly stimulates cell proliferation and differentiation of osteoblasts; therefore, this study preliminarily explored the pharmacological mechanism of PAF to promote the healing of bone rheumatism and various fractures.

Bone changes and fracture risk in individuals infected with HIV.

The life expectancy of individuals infected with HIV has improved greatly since the institution of combination antiretroviral therapy. However, many metabolic derangements have been discovered with long-term combination antiretroviral treatment, including lipodystrophy; insulin resistance; and, more recently, abnormal bone metabolism. It is well-documented that bone mineral density (BMD) in HIV-positive patients is lower compared with the expected BMD in non-HIV-positive patients. The underlying cause of lower BMD is unknown but is thought to be a multifactorial process. Conflicting evidence exists regarding the effect of antiretroviral exposure and duration of treatment, antiretroviral type, and cumulative HIV viral exposure on bone health. Here we review the bone changes that occur with HIV infection and treatment.

[Secondary osteoporosis UPDATE. Pathophysiology and management of cancer treatment-induced bone loss/fractures].

Patients with cancers such as breast or prostate cancer who have been treated with hormone deprivation therapies or anti-cancer agents for certain periods of time frequently manifest reduced bone mass or pathological fractures during their clinical course. These are likely due to an imbalance between osteoblastic bone formation and osteoclastic bone resorption resulting from hypogonadism. Bone should be carefully monitored in cancer patients who are going to continually receive adjuvant hormonal or anti-cancer therapies. Administration of anti-bone resorption agents such as bisphosphonates may be necessary to maintain bone mineral density and protect pathological fractures in these cancer patients.

Vitamin D binding protein genotype and osteoporosis.

Osteoporosis is a bone disease leading to an increased fracture risk. It is considered a complex multifactorial genetic disorder with interaction of environmental and genetic factors. As a candidate gene for osteoporosis, we studied vitamin D binding protein (DBP, or group-specific component, Gc), which binds to and transports vitamin D to target tissues to maintain calcium homeostasis through the vitamin D endocrine system. DBP can also be converted to DBP-macrophage activating factor (DBP-MAF), which mediates bone resorption by directly activating osteoclasts. We summarized the genetic linkage structure of the DBP gene. We genotyped two single-nucleotide polymorphisms (SNPs, rs7041 = Glu416Asp and rs4588 = Thr420Lys) in 6,181 elderly Caucasians and investigated interactions of the DBP genotype with vitamin D receptor (VDR) genotype and dietary calcium intake in relation to fracture risk. Haplotypes of the DBP SNPs correspond to protein variations referred to as Gc1s (haplotype 1), Gc2 (haplotype 2), and Gc1f (haplotype3). In a subgroup of 1,312 subjects, DBP genotype was found to be associated with increased and decreased serum 25-(OH)D(3) for haplotype 1 (P = 3 x 10(-4)) and haplotype 2 (P = 3 x 10(-6)), respectively. Similar associations were observed for 1,25-(OH)(2)D(3). The DBP genotype was not significantly associated with fracture risk in the entire study population. Yet, we observed interaction between DBP and VDR haplotypes in determining fracture risk. In the DBP haplotype 1-carrier group, subjects of homozygous VDR block 5-haplotype 1 had 33% increased fracture risk compared to noncarriers (P = 0.005). In a subgroup with dietary calcium intake <1.09 g/day, the hazard ratio (95% confidence interval) for fracture risk of DBP hap1-homozygote versus noncarrier was 1.47 (1.06-2.05). All associations were independent of age and gender. Our study demonstrated that the genetic effect of the DBP gene on fracture risk appears only in combination with other genetic and environmental risk factors for bone metabolism.

[Fractures and chronic renal insufficiency]. / La patologia fratturativa nei diversi gradi di insufficienza renale cronica.

Chronic renal insufficiency (CRI) causes important modifications in the metabolism of phosphorus and calcium, to which frequently resulting in serious disorders of the skeleton, including demineralization, reduction of the bone resistance and a higher risk of fractures. Renal osteodystrophy is the term used to describe these disorders; they are generally heterogeneous and are classified according to the state of bone turnover into secondary hyperparathyroidism, adynamic bone, and osteomalacia. The incidence of hip fractures in the patients with CRI is higher than in the general population. Hip fractures are an important cause of morbidity and mortality. The evaluation of the fracture risk in the patients with different degrees of CRI is problematic, in particular because of the difficulty in identifying fractures, especially vertebral ones. The instrumental index that best expresses the fracture risk in the general population is bone mineral density (BMD); however, the relationship between low BMD and CRI is disputed. Bone disorders in patients with CRI have in fact a multifactorial pathogenesis and low BMD is not the only risk factor for fractures. Besides densitometric evaluation, also that vertebral morphometric evaluation would be desirable in patients with CRI. The fracture risk increases progressively with the severity of chronic renal disease and it is especially high in patients with renal insufficiency in more advanced-stages CRI (creatinine clearance<15-20 mL/min). However, not only in patients with severe CRI undergoing dialysis, but also in those with milder renal disease is the risk of bone fractures high.

Identification of an aromatase haplotype that is associated with gene expression and postmenopausal osteoporosis.

CONTEXT: Osteoporosis has a significant genetic component. The aromatase-dependent conversion of androgenic precursors is the main source of estrogens in postmenopausal women. OBJECTIVE: The objective of the investigation was to study the relationship of a set of single nucleotide polymorphisms (SNPs) of the aromatase gene with osteoporosis and determine their functional influence on gene transcription. DESIGN, PARTICIPANTS, AND METHODS: This was a case-control study including 135 women with vertebral fractures due to postmenopausal osteoporosis and 312 controls. Alleles at four SNPs situated between exons I.2 and 3 were determined by Taqman assays. Total aromatase RNA and differential allelic-specific expression were studied by RT-real time PCR in adipose tissue samples taken from 50 individuals. RESULTS: The SNPs studied were in strong linkage disequilibrium. A common haplotype, present in about half of the population, was identified as being associated with an increased risk of fractures (odds ratio 1.8, 95% confidence interval 1.2-2.8, P = 0.006). There was evidence of differential allelic expression. In heterozygous individuals, transcripts bearing T alleles at rs700518 SNP (which were included in the risk haplotype) were less abundant than those with the alternative C alleles (P < 0.001). Total aromatase expression was four times lower in fat samples from individuals who were homozygotes for the unfavorable alleles than in the opposite homozygotes (P = 0.007). CONCLUSIONS: A common haplotype of aromatase associated with gene expression is also associated with the risk of osteoporotic vertebral fractures in postmenopausal women. These data are in line with the hypothesis that the aromatase-dependent synthesis of estrogens plays an important role in bone homeostasis in postmenopausal women.

Statins in rheumatology.

Statins were developed for the treatment of lipid disorders and have been proved to reduce cardiovascular morbidity and mortality when used for primary or secondary prevention. Beneficial effects in patients with osteoporotic fractures or rheumatoid arthritis (RA) have been suggested but remain unproven. Cardiovascular morbidity and mortality are increased in patients with RA or systemic lupus erythematosus, who should undergo serum lipid assays. When these show dyslipidemia, statin therapy should be started according to current recommendations.

A method for determining the grade of osteoporosis based on risk factors in postmenopausal women.

The aim of this study was to determine whether the probability of osteoporosis and osteopenia was affected by the risk factors, physical examination findings, or radiological investigations such as spinal X-rays in postmenopausal women. We assessed risk factors such as use of hormone replacement therapy, physical activity level, calcium intake, smoking, caffeine consumption, long-term immobilization, previous history of fracture, family history of fracture, presence of certain systemic diseases (hyperthyroidism or hyperparathyroidism), or use of medications (corticosteroids or others), physical examinations, and presence of vertebral fractures on spinal X-rays. Patients' bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry (DXA) in the lumbar spine, and we compared the risk factors between osteopenic and osteoporotic women according to DXA. We evaluated 235 postmenopausal women who attended our osteoporosis outpatient clinic. Those patients were divided into two groups as either osteopenic (n = 67, mean age: 63.1 years) or osteoporotic (n = 168, mean age: 66.2 years) according to WHO criteria. The lumbar spinal (L1-L2) T-score values were -1.5 +/- 0.6 and -3.1 +/- 0.6 in osteopenic and osteoporotic groups, respectively. There were significant differences between the two groups in terms of mean age and lumbar BMD (p = 0.009 and p < 0.001, respectively). We also observed that vertebral tenderness on palpation, back pain, and existing vertebral fracture (fx) were significantly different between the osteopenic and osteoporotic groups (p < 0.05). As a result of the statistical analysis, we found an equation to determine osteopenic and osteoporotic women by using those four factors (age, vertebral tenderness on palpation, back pain, and existing vertebral fx) in multivariate stepwise logistic regression. The equation is as follows: Y (DXA) = -2.9024 + 0.044 (age in year) + 0.819 (vertebral fx) + 0.877 (pain) + 1.136 (vertebral tenderness). We can estimate whether a postmenopausal woman is osteopenic or osteoporotic based on these risk factors by using the stepwise logistic regression equation.

Fracture history and bone loss in patients with MS.

OBJECTIVES: We have previously shown that MS patients have significantly reduced bone mass and a high prevalence of abnormal vitamin D status. The object of this study was to characterize the frequency of adulthood fractures in MS patients, prospectively determine rates of bone loss in MS, and determine whether vitamin D status is a predictor of bone loss. METHODS: MS patients (36 women, 18 men) were compared with age- and gender-matched healthy controls (35 women, 14 men). Bone mass was performed by dual x-ray absorptiometry at baseline and at 12-month intervals over 2 years. RESULTS: Fractures in the absence of major trauma had occurred in 2% of controls and 22% of MS patients (p < 0.002). Over the 2 years of prospective follow-up, both women and men with MS lost substantially more bone in the femoral neck than did controls (3% and 6% per year in pre- and postmenopausal women with MS versus 0.5% and 0.8% per year in controls; 7.3% per year in men with MS versus 1.6% per year in controls). Bone loss in the spine was also greater in women with MS than in controls (1.6 to 3.5% per year loss in MS patients versus no change in controls). Duration of steroid treatment beyond 5 months and ambulatory status were both predictors of bone loss. Bone loss in the spine occurred faster in MS patients with low (<20 ng/mL) 25-hydroxyvitamin D levels (1.9% per year, p < 0.04), whereas in those with normal 25-hydroxyvitamin D levels, bone loss was insignificant. At the femoral neck, bone loss was substantial in all patients, but was somewhat faster in the group with low levels of 25-hydroxyvitamin D (5.6% per year, p < 0.0001) compared with the group with high levels of 25-hydroxyvitamin D (4.3% per year, p = 0.03). CONCLUSIONS: MS patients have more frequent fractures and lose bone mass more rapidly than do their healthy age- and gender-matched peers, in part related to insufficient vitamin D. Vitamin D repletion in MS patients who are deficient might reduce, to some extent, the rate of bone loss and decrease osteoporosis-related fractures.

Association between endogenous hormones and sex hormone-binding globulin and bone turnover in older women: study of osteoporotic fractures.

Estrogen therapy decreases bone remodeling, but the association between endogenous estradiol (E2), estrone (E1), testosterone (T), and bone turnover in older women is not clear. To test the association of serum E2, E1, free T, and sex hormone-binding globulin (SHBG) with bone turnover, we analyzed cross-sectional relationships among E2, E1, T, SHBG, and biochemical markers of bone turnover serum osteocalcin [OC], serum bone-specific alkaline phosphatase [bAP], and serum breakdown products of C telopeptide of type I collagen [CTx] in 704 women enrolled in the Study of Osteoporotic Fractures. Women with lower estradiol levels tended to have higher levels of bone turnover, but the association was weak (R(2) = 0.01 for the association E2-OC, p = 0.03; and R(2) = 0.024 for E2-CTx, p = 0.001). Relationships between SHBG and turnover were also weak (R(2) for the association SHBG-OC was 0.07, p < 0.001, and 0.03 for SHBG-sCTx, p = 0.03), or not significant (R(2) < 0.01 for the association SHBG-bAP). Associations of E1 and T with these markers were of the same magnitude. These results were not modified after adjustment for age, weight, and smoking status. We conclude that older women with low endogenous hormones have somewhat higher bone turnover, but these associations are weak. Bone turnover is determined mainly by factors other than endogenous concentrations of sex hormones.

Sequential serum aluminum and urine aluminum: creatinine ratio and tissue aluminum loading in infants with fractures/rickets.

Aluminum toxicity is associated with the development of bone disorders, including fractures, osteopenia, and osteomalacia. Fifty-one infants with a mean (+/- SEM) birth weight of 1007 +/- 34 g, gestational age of 28.5 +/- 0.3 weeks, and serial radiographic documentation at 3, 6, 9, and 12 months for the presence (n = 16) or absence (n = 35) of fractures and/or rickets were studied at the same intervals to determine the serial changes in serum aluminum concentrations and urine aluminum-creatinine ratios. Autopsy bone samples were used to determine the presence of tissue aluminum. Serum aluminum concentrations from 46 infants were stable and similar between groups, with mean values between 15 and 22 micrograms/L. Urine aluminum-creatinine (micrograms per milligram) ratios from 14 infants were higher in infants with fractures and/or rickets (0.26 +/- 0.06 vs 0.12 +/- 0.04) at onset, and rate of decrease in aluminum-creatinine ratio was faster in infants without fractures and/or rickets. All but three infants were tolerating complete enteral feeding at all sampling points. One infant who received aluminum-containing antacid had marked increase in serum aluminum to 83 micrograms/L while urine aluminum-creatinine ratio increased from 0.09 to a peak of 8.53. Vertebrae from three infants at autopsy (full enteral feeding was tolerated for 37 and 41 days in two infants, respectively) showed aluminum deposition in the zone of provisional calcification and along the newly formed trabecula.(ABSTRACT TRUNCATED AT 250 WORDS)

A human cadaver model for determination of pathologic fracture threshold resulting from tumorous destruction of the vertebral body.

STUDY DESIGN: Thoracic vertebrae were subjected to compressive loads after drilling of the centrum to simulate destruction from metastatic tumorous involvement. OBJECTIVE: To determine whether a threshold exists that is predictive of fractures to establish a correlation between significant variables and vertebral strength. SUMMARY OF BACKGROUND DATA: The mechanical effects of metastatic destruction of thoracic vertebral bodies and their correlation to pathologic fractures has been analyzed in few studies. In additional studies on intact vertebral strength, investigators have determined that bone mineral density and geometric factors are important. METHOD: Fifty-four cadaveric thoracic vertebrae were studied. All were examined by quantitative computed tomography. T4 and T10 served as mechanical controls to predict the intact strength of T7. The test vertebrae were drilled from the anterior cortex through to the posterior cortex before they were loaded. RESULTS: Linear correlation between the strength of T4 and T10 in each spine supported the predicted strengths of T7. Because of variation from other factors, no threshold defect size was noted beyond which failure consistently occurred. Results of linear correlation analyses showed that the best combination of parameters for predicting vertebral strength was the product of bone mineral density and the remaining intact vertebral body cross-sectional area. This vertebral strength index correlated linearly with the strength of intact and compromised T7 vertebrae (r2 = 0.52). CONCLUSIONS: The vertebral strength index can be used to predict the strength of any thoracic vertebra. When compared with an idealized vertebral strength index based on the intact vertebral cross-sectional area and normal bone mineral density, a patient's actual vertebral strength index can be used as one of the criteria for prophylactic stabilization.

In vivo measurement of apparent trabecular bone structure of the radius in women with low bone density discriminates patients with recent wrist fracture from those without fracture.

The purpose of this cross-sectional case-control study was to determine whether indices of bone structure at the 4% site of the radius discriminate women who have sustained a recent low-energy fracture of the contralateral distal radius (n = 21) from women with similar bone density and no history of fracture (n = 21). Images of the distal forearm were acquired using peripheral quantitative computed tomography (pQCT) and were analyzed using in-house-developed software to determine indices of trabecular bone structure (average hole size [H(A)], maximum hole size, and connectivity index). The same images were analyzed using commercial software to determine bone density, mass, geometry, and torsional strength. The fracture group had significantly larger H(A) (p = 0.03). No other bone variable differed between groups. Individual H(A) values were compared to the mean value for young adult women (n = 42). The odds ratio (95% confidence interval) associated with an H(A) >2 SDs above the young adult mean was 5.4 (1.2-24.3). Thus, estimation of in vivo trabecular bone porosity by measuring the average diameter of the pQCT-imaged marrow spaces in the ultradistal radius identifies individuals with low bone mass most at risk for osteoporotic fracture.

Osteolysis of the pelvis presenting as insufficiency fracture in a patient with rheumatoid arthritis.

Physician awareness of the risk of osteoporosis and subsequent fractures in a patient with a history of long-term steroid treatment is high. The tendency to assume that a fracture is owing to steroid-induced osteoporosis may result in an unnecessarily intense antiresorptive treatment regimen for a patient who may not have osteoporosis. I report here about a patient with rheumatoid arthritis who presented with bone fracture despite antiresorptive therapy and without evidence of osteoporosis by bone mineral density testing.