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A 58-yr-old woman presented to our mineral metabolism center, complaining of localized and continuous pain, which worsened with movements, and weakness of the right foot. The patient reported having had a fracture of the fifth metatarsal bone of the right foot about 4 mo ago. She was initially treated with a cast that she did not tolerate and then with an orthopedic brace. After about 1 mo, she noticed swelling of the right foot and started complaining of continuous pain. The physical examination when came to our center seemed partly improved in respect to the initial one referred by the patient even though she still presented with a mild swelling, reddish skin color, and mild sweating on the right foot. Allodynia and hyperalgesia still persisted but at a lower grade. Main biochemical parameters of calcium metabolism were in the normal range. After excluding other clinical conditions, a diagnosis of complex regional pain syndrome type I was made. She was treated with neridronate iv with resolution of symptoms while continuing with physical therapy and pain relievers. Similar milder episodes were reported by the patient in the following months. However, they were immediately resolved by prompt neridronate infusion. No further complaints have been reported during the next 3 yr follow-up., (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The validity of prognostic nutritional index (PNI) as an index of incident bone fragility fracture (inc-BFF) in rheumatoid arthritis (RA) patients was investigated., Methods: RA patients whom continuously followed up for >3 years were picked up. Patients were classified in accordance with inc-BFF positivity (BFF+ and BFF-). Their clinical background including PNI was statistically examined for inc-BFF. The background factors were compared between the two groups. Patients were narrowed into subgroups according to the factor that showed a significant difference between the two groups, and they were statistically examined according to the PNI for the inc-BFF. The two groups were narrowed with propensity score matching and compared to the PNI., Results: A total of 278 patients with 44 BFF+ and 234 BFF- were recruited. In the background factors, the presence of prevalent BFF and the simplified disease activity index remission rate had a significantly higher risk ratio. In a subgroup who comorbid lifestyle-related diseases, PNI had a significantly higher risk ratio for the inc-BFF. After the propensity score matching, the PNI showed no significant difference between the two groups., Conclusions: PNI is available when patients with RA comorbid lifestyle-related diseases. PNI is not an independent key for the inc-BFF in RA patients., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abdominal aortic calcification (AAC), a recognized measure of advanced vascular disease, is associated with higher cardiovascular risk and poorer long-term prognosis. AAC can be assessed on dual-energy X-ray absorptiometry (DXA)-derived lateral spine images used for vertebral fracture assessment at the time of bone density screening using a validated 24-point scoring method (AAC-24). Previous studies have identified robust associations between AAC-24 score, incident falls, and fractures. However, a major limitation of manual AAC assessment is that it requires a trained expert. Hence, we have developed an automated machine-learning algorithm for assessing AAC-24 scores (ML-AAC24). In this prospective study, we evaluated the association between ML-AAC24 and long-term incident falls and fractures in 1023 community-dwelling older women (mean age, 75 ± 3 years) from the Perth Longitudinal Study of Ageing Women. Over 10 years of follow-up, 253 (24.7%) women experienced a clinical fracture identified via self-report every 4-6 months and verified by X-ray, and 169 (16.5%) women had a fracture hospitalization identified from linked hospital discharge data. Over 14.5 years, 393 (38.4%) women experienced an injurious fall requiring hospitalization identified from linked hospital discharge data. After adjusting for baseline fracture risk, women with moderate to extensive AAC (ML-AAC24 ≥ 2) had a greater risk of clinical fractures (hazard ratio [HR] 1.42; 95% confidence interval [CI], 1.10-1.85) and fall-related hospitalization (HR 1.35; 95% CI, 1.09-1.66), compared to those with low AAC (ML-AAC24 ≤ 1). Similar to manually assessed AAC-24, ML-AAC24 was not associated with fracture hospitalizations. The relative hazard estimates obtained using machine learning were similar to those using manually assessed AAC-24 scores. In conclusion, this novel automated method for assessing AAC, that can be easily and seamlessly captured at the time of bone density testing, has robust associations with long-term incident clinical fractures and injurious falls. However, the performance of the ML-AAC24 algorithm needs to be verified in independent cohorts. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Postoperative hypoparathyroidism (PO-hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. Although long-term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO-hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy, was analyzed using the multivariable Cox proportional hazard model. The PO-hypoPT and preserved parathyroid function groups included 8789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow-up duration of 4.8 years, 159 (1.8%) and 2390 (2.2%) fractures occurred in the PO-hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO-hypoPT group than in the preserved parathyroid function group (hazard ratio [HR] = 0.83; 95% confidence interval [CI] 0.70-0.98; p = 0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO-hypoPT group compared with the preserved parathyroid function group (HR = 0.67; 95% CI 0.47-0.96; p = 0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO-hypoPT and the risk of any fractures (p for interactions = 0.010 and 0.017, respectively). PO-hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO-hypoPT and appropriate management for PO-hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long-term overtreatment with levothyroxine. © 2023 American Society for Bone and Mineral Research (ASBMR)., (© 2023 American Society for Bone and Mineral Research (ASBMR).)

Background: While the impact of female sexual dysfunction (FSD) on mental health and overall health-related quality of life (HrQOL) has been previously documented, no prior work has evaluated this relationship in women following traumatic pelvic injuries., Aim: This study aims to understand the relationship of FSD with HrQOL and depression in women with a history of traumatic pelvic fracture., Methods: Data were collected with an electronic survey that included queries regarding mental and sexual health. Inverse probability weighting and multivariate regression models were utilized to assess the relationships between sexual dysfunction, depression and HrQOL., Outcomes: Study outcome measures included the Female Sexual Function Index (FSFI) to evaluate sexual functioning, the 8-item patient health questionnaire (PHQ-8) to assess depression symptoms, and the visual analog scale (VAS) component of the EuroQol 5 Dimensions Questionnaire (EQ-5D) to determine self-reported HrQOL., Results: Women reporting FSD had significantly higher PHQ-8 scores with a median PHQ-8 score of 6 (IQR 2, 11) relative to those without FSD who had a median score of 2 (IQR 0, 2) (P < .001). On multivariate linear regression, presence of FSD was significantly associated with higher PHQ-8 scores (β = 4.91, 95% CI 2.8-7.0, P < .001). FSFI score, time from injury, and age were all independently associated with improved HrQOL, with FSFI having the largest effect size (β = 0.62, 95% CI 0.30-0.95, P < .001)., Clinical Implications: These results underscore importance of addressing not just sexual health, but also mental health in female pelvic fracture survivors in the post-injury setting., Strengths and Limitations: This study is one of the first to examine women with traumatic pelvic fractures who did not sustain concomitant urinary tract injuries. Study limitations include low response rate and the inherent limitations of a cross-sectional study design., Conclusion: Patients with persistent, unaddressed FSD after pelvic fracture are at unique risk for experiencing depression and reporting worse health-related quality of life due to complex biopsychosocial mechanisms. Gambrah HA, Hagedorn JC, Dmochowski RR, et al. Sexual Dysfunction in Women after Traumatic Pelvic Fracture Negatively Affects Quality of Life and Mental Health. J Sex Med 2022;19:1759-1765., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) patients present with symptoms such as impairment of insulin signaling, chronic inflammation, and oxidative stress. Furthermore, there are comorbidities associated with AD progression. For example, osteoporosis is common with AD wherein patients exhibit reduced mineralization and a risk for fragility fractures. However, there is a lack of understanding on the effects of AD on bone beyond loss of bone density. To this end, we investigated the effects of AD on bone quality using the 5XFAD transgenic mouse model in which 12-month-old 5XFAD mice showed accumulation of amyloid-beta (Aβ42) compared with wild-type (WT) littermates (n = 10/group; 50% female, 50% male). Here, we observed changes in cortical bone but not in cancellous bone quality. Both bone mass and bone quality, measured in femoral samples using imaging (micro-CT, confocal Raman spectroscopy, X-ray diffraction [XRD]), mechanical (fracture tests), and chemical analyses (biochemical assays), were altered in the 5XFAD mice compared with WT. Micro-CT results showed 5XFAD mice had lower volumetric bone mineral density (BMD) and increased endocortical bone loss. XRD results showed decreased mineralization with smaller mineral crystals. Bone matrix compositional properties, from Raman, showed decreased crystallinity along with higher accumulation of glycoxidation products and glycation products, measured biochemically. 5XFAD mice also demonstrated loss of initiation and maximum toughness. We observed that carboxymethyl-lysine (CML) and mineralization correlated with initiation toughness, whereas crystal size and pentosidine (PEN) correlated with maximum toughness, suggesting bone matrix changes predominated by advanced glycation end products (AGEs) and altered/poor mineral quality explained loss of fracture toughness. Our findings highlight two pathways to skeletal fragility in AD through alteration of bone quality: (i) accumulation of AGEs; and (ii) loss of crystallinity, decreased crystal size, and loss of mineralization. We observed that the accumulation of amyloidosis in brain correlated with an increase in several AGEs, consistent with a mechanistic link between elevated Aβ42 levels in the brain and AGE accumulation in bone. © 2022 American Society for Bone and Mineral Research (ASBMR)., (© 2022 American Society for Bone and Mineral Research (ASBMR).)

The objective of this work was to estimate the incidence rate of cardiovascular disease (CVD) events (myocardial infarction, stroke, or CVD death) at 1 year among three cohorts of patients at high risk of fracture (osteoporosis, previous fracture, and anti-osteoporosis medication) and to identify the key risk factors of CVD events in these three cohorts. To do so, this prospective cohort study used data from the Clinical Practice Research Datalink, a primary care database from United Kingdom. Major adverse cardiovascular events (MACE, a composite outcome for the occurrence of either myocardial infarction [MI], stroke, or CVD death) were identified in patients aged 50 years or older at high or imminent fracture risk identified in three different cohorts (not mutually exclusive): recently diagnosed with osteoporosis (OST, n = 65,295), incident fragility fracture (IFX, n = 67,065), and starting oral bisphosphonates (OBP, n = 145,959). About 1.90%, 4.39%, and 2.38% of the participants in OST, IFX, and OBP cohorts, respectively, experienced MACE events. IFX was the cohort with the higher risk: MACE incidence rates (cases/1000 person-years) were 19.63 (18.54-20.73) in OST, 52.64 (50.7-54.5) in IFX, and 26.26 (25.41-27.12) in OBP cohorts. Risk of MACE events at 1 year was predicted in the three cohorts. Models using a set of general, CVD, and fracture candidates selected by lasso regression had a good discrimination (≥70%) and internal validity and generally outperformed the models using only the CVD risk factors of general population listed in QRISK tool. Main risk factors common in all MACE models were sex, age, smoking, alcohol, atrial fibrillation, antihypertensive medication, prior MI/stroke, established CVD, glomerular filtration rate, systolic blood pressure, cholesterol levels, and number of concomitant medicines. Identified key risk factors highlight the differences of patients at high risk of fracture versus general population. Proposed models could improve prediction of CVD events in patients with osteoporosis in primary care settings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Accumulation of advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean ± standard deviation (SD) age was 73.7 ± 2.8 and 73.6 ± 2.9 years in T2D (n = 712) and non-diabetes (n = 2332), respectively. Baseline CML levels were higher in T2D than non-diabetes (893 ± 332 versus 771 ± 270 ng/mL, p < 0.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24-1.79 per 1-SD increase in log CML) but not in non-diabetes (HR 1.03; 95% CI, 0.94-1.13; p for interaction = 0.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin-C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone and endocrine disorder arising along a broad spectrum. Long-bone fractures are a common, painful, and potentially disabling complication. However, fracture prevalence and risk factors have not been well-established, making it difficult to predict which patients are at risk for a severe course. Clinical and imaging data were reviewed from two large, well-phenotyped cohorts (National Institutes of Health [NIH] in the United States and the Leiden University Medical Center [LUMC] in the Netherlands) to identify long-bone fractures at FD sites. Skeletal burden score was quantified using bone scintigraphy. Multiple linear regressions were performed to identify clinical associations with fractures. A total of 419 patients were included (186 NIH, 233 LUMC); 194 (46%) had MAS endocrinopathies. Median age at last follow-up was 30.2 years (range 3.2-84.6, interquartile range [IQR] 25.5), and median skeletal burden score was 16.6 (range 0-75, IQR 33). A total of 48 (59%) patients suffered one or more lifetime fracture (median 1, range 0-70, IQR 4). Median age at first fracture was 8 years (range 1-76, IQR 10). Fracture rates peaked between 6 and 10 years of age and decreased thereafter. Lifetime fracture rate was associated with skeletal burden score (β = 0.40, p < 0.01) and MAS hyperthyroidism (β = 0.22, p = 0.01). Younger age at first fracture was associated with skeletal burden score (β = -0.26, p = 0.01) and male sex (β = -0.23, p = 0.01). Both skeletal burden score >25 and age at first fracture ≤7 years were associated with a higher total number of lifetime fractures (median 4, range 1-70, IQR 5 versus median 1, range 1-13, IQR 1) (p < 0.01). In conclusion, higher skeletal burden score and MAS hyperthyroidism are associated with long-bone fractures in FD/MAS. Both skeletal burden score ≥25 and age at first fracture ≤7 years are associated with a higher lifetime long-bone fracture risk and may predict a more severe clinical course. These results may allow clinicians to identify FD/MAS patients at risk for severe disease who may be candidates for early therapeutic interventions. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA., (© 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Multiple myeloma is a plasma cell malignancy that causes debilitating bone disease and fractures, in which TGFβ plays a central role. Current treatments do not repair existing damage and fractures remain a common occurrence. We developed a novel low tumor phase murine model mimicking the plateau phase in patients as we hypothesized this would be an ideal time to treat with a bone anabolic. Using in vivo μCT we show substantial and rapid bone lesion repair (and prevention) driven by SD-208 (TGFβ receptor I kinase inhibitor) and chemotherapy (bortezomib and lenalidomide) in mice with human U266-GFP-luc myeloma. We discovered that lesion repair occurred via an intramembranous fracture repair-like mechanism and that SD-208 enhanced collagen matrix maturation to significantly improve fracture resistance. Lesion healing was associated with VEGFA expression in woven bone, reduced osteocyte-derived PTHrP, increased osteoblasts, decreased osteoclasts, and lower serum tartrate-resistant acid phosphatase 5b (TRACP-5b). SD-208 also completely prevented bone lesion development in mice with aggressive JJN3 tumors, and was more effective than an anti-TGFβ neutralizing antibody (1D11). We also discovered that SD-208 promoted osteoblastic differentiation (and overcame the TGFβ-induced block in osteoblastogenesis) in myeloma patient bone marrow stromal cells in vitro, comparable to normal donors. The improved bone quality and fracture-resistance with SD-208 provides incentive for clinical translation to improve myeloma patient quality of life by reducing fracture risk and fatality. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Zoledronic acid (ZOL) 5 mg annually was more effective than tenofovir disoproxil fumarate (TDF) switching at increasing bone mineral density (BMD) over 24 months in HIV-infected, osteopenic adults. To determine whether the effects of ZOL would persist without further infusions, we compared changes in left hip and spine BMD over 36 months in participants randomized to ZOL 5 mg at baseline and month 12 (and to continue TDF) or to switch TDF (without receiving ZOL). We also compared changes in the plasma bone turnover markers (BTMs) C-terminal telopeptide of type 1 collagen (CTX; bone resorption), and procollagen type 1 N propeptide (P1NP; bone formation) and determined whether CTX and P1NP changes at month 3 predicted BMD changes at month 36. Changes were compared in the per-protocol populations, which included 32 (74%) of 43 participants randomized to ZOL and 37 (88%) of 42 participants who switched TDF. Despite not receiving ZOL after month 12, mean hip and spine BMD change from baseline were stable and remained greater with ZOL at month 36 than with TDF switching (spine: 7.5% versus 2.7%, mean difference 4.7%, p < 0.001; hip: 5.5% versus 1.5%, mean difference 4.0%, p < 0.001). CTX and P1NP levels declined in both groups but significantly more with ZOL. Only percent changes in P1NP at month 3 correlated inversely with BMD changes at month 36 (spine: rho = -0.442, p < 0.001; hip: rho = -0.373, p = 0.002). Two infusions of ZOL (in the presence of ongoing TDF) yielded sustained BMD increases through month 36 that remained greater than with TDF switching. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Musculoskeletal pain is common and typically occurs at multiple sites. Pain has been shown to be associated with falls risk; however, whether an increased risk for falls associated with multisite pain (MSP) translates into an increased risk of fractures has not been investigated. This study aimed to examine the association of number of painful sites with prevalent and incident fractures. Data from a longitudinal population-based study of older adults (mean age 63 years) were utilized. Follow-up was performed at 2.6, 5.1, and 10.7 years later, respectively. Presence/absence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire at baseline. Participants were classified into three groups according to the total number of painful sites: zero to two, three to four, and five to seven. Fractures were self-reported at each time point. BMD was measured by DXA. Falls risk was calculated based on the Short-Form Physiological Profile Assessment. Log-binomial regression was used for the analyses. There were 450 fractures at baseline and 154 new fractures reported during a mean follow-up period of 10.7 years (range 9.2 to 12.5 years). In multivariable analyses, number of painful sites was associated with prevalent fractures at any and nonvertebral site. Furthermore, participants with five to seven painful sites had an increased risk of incident fractures at any site (RR 1.69; 95% CI, 1.13 to 2.53); major site, including the femur, radius, ulnar, vertebral, rib, and humerus (RR 2.17; 95% CI 1.12 to 4.22); and vertebral site (RR 6.44, 95% CI, 1.64 to 25.33) compared with those with pain at zero to two sites. These associations remained statistically significant after further adjustment for falls risk and BMD. Pain at multiple sites was associated with incident fracture risk in a dose-response manner, suggesting that widespread pain is an independent contributor to fracture risk. The potential for pain management in fracture prevention warrants further exploration. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Introduction: Traumatic pelvic fractures are associated with sexual dysfunction in men. However, how men are counseled and access care for sexual health following injury remains unknown., Aim: The purpose of this study was to identify factors associated with accessing and obtaining care for sexual health concerns following traumatic pelvic fracture in men., Methods: Men treated for traumatic pelvic fractures at a level 1 trauma center were invited to participate in an online cross-sectional survey. The survey addressed multiple demographic and sexual function domains, as well as the postinjury sexual health care experience. De novo sexual dysfunction following injury was ascertained and reasons for not seeking care examined. Inverse probability weighting was utilized to adjust for nonresponse. Multivariable logistic regression was performed to identify factors associated with discussion of sexual health with providers after injury., Outcomes: The primary outcome was discussion of sexual health with health care providers after injury. Secondary outcomes included prevalence of self-reported sexual dysfunction, classification of sexual dysfunction experienced, and perceived barriers to accessing or obtaining care for sexual health concerns., Results: 277 men completed the survey. After adjustment, 46.3% (95% CI = 39.4%-53.0%) reported de novo sexual dysfunction after injury, with erectile dysfunction the most common symptom (27.9%). Only 20.4% (95% CI = 15.1%-26.0%) recalled having discussions or being asked about their sexual health following injury, and of these conversations 70.7% were patient-initiated. The most common perceived barriers to discussing sexual health with providers were the belief that sexual dysfunction would resolve with time (26.1%), and a lack of knowledge about their condition and treatment options (21.5%). On multivariate analysis, the presence of postinjury sexual dysfunction (adjusted odds ratio [aOR] = 3.42), private insurance (aOR = 2.17), and being married or in a partnership (aOR = 3.10) were independently associated with likelihood of having had sexual health discussions., Clinical Implications: Despite the high prevalence of sexual dysfunction in men following pelvic trauma, sexual health concerns are inadequately addressed due to both patient and provider factors., Strengths & Limitations: The major strengths include large sample size, detailed reporting of subject experience, and new information in a previously understudied area of pelvic trauma survivorship. The primary limitations are low survey response rate, lack of representativeness of survey participants to whole pelvic fracture cohort, single-center experience, and cross-sectional study design., Conclusion: Sexual health concerns after pelvic fracture are common but inadequately addressed by health care providers. Improved postinjury, survivorship-model care pathways need to be designed to better address sexual health after injury. Johnsen NV, Lang J, Wessells H, et al. Barriers to Care of Sexual Health Concerns in Men Following Traumatic Pelvic Fractures. J Sex Med 2019;16:1557-1566., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Disseminated cryptococcosis caused by Cryptococcus gattii (molecular type VGI) was diagnosed in an adult free-ranging female koala (Phascolarctos cinereus). Subclinical cryptococcosis was later diagnosed in this koala's joey. In the adult koala, a pathological fracture of the tibia was associated with the bone lysis of marked focal cryptococcal osteomyelitis. Limb-sparing orthopedic intervention, in the setting of disseminated cryptococcosis, was judged to have a poor prognosis, and the adult koala was euthanized. The joey was removed and hand-reared. Serological testing revealed persistent and increasing cryptococcal capsular antigenemia in the absence of clinical signs of disease and it was subsequently treated with oral fluconazole for approximately 16 months, rehabilitated and released into the wild. It was sighted 3 months post-release in a good state of health and again at 18 months post-release but was not recaptured on either occasion. This is the first published report of cryptococcal appendicular osteomyelitis in a koala. It is also the first report of concurrent disease in a dependent juvenile and the successful treatment of subclinical cryptococcosis to full resolution of the cryptococcal antigenemia in a free-ranging koala. This paper provides a discussion of cryptococcal osteomyelitis in animals, host-pathogen-environment interactions and treatment and monitoring protocols for cryptococcosis in koalas. Published reports describing the treatment of cryptococcosis in koalas are also collated and summarised.

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was incomplete or absent in 22.7% of children. Those with residual vertebral deformity following VF were older compared to those without (median age 8.0 years at baseline [interquartile range {IQR}, 5.5 to 9.4] versus 4.8 years [IQR, 3.6 to 6.2], p = 0.04) and had more severe vertebral collapse (median maximum spinal deformity index 3.5 [IQR, 1.0 to 8.0] versus 0.5 [IQR, 0.0 to 1.0], p = 0.01). VF and low LS BMD Z-score at baseline as well as glucocorticoid exposure predicted incident VF and non-VF. Nearly 25% of children had persistent vertebral deformity following VF, more frequent in older children, and in those with more severe collapse. These results suggest the need for trials addressing interventions in the first 2 years of chemotherapy, targeting older children and children with more severe vertebral collapse, because these children are at greatest risk for incident VF and subsequent residual vertebral deformity. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Objective: To assess the extent of pelvic hemorrhage on CT and to estimate its significance on outcome in patients with blunt high-energy pelvic trauma., Methods: 576 patients with blunt high-energy pelvic fractures in 2005-2011 were identified in the hospital's Trauma Registry (a major Trauma Center). 60 of these met our further inclusion criteria of initial systolic blood pressure ≤100 mmHg and pelvic-related hemorrhage. CT scans of the patients were reviewed with regard to pelvic and abdominal retroperitoneal hemorrhage, type of fracture (Tile classification) and associated injuries. Extent of hemorrhage was correlated to 30-day mortality, transfusion requirements and need of angiography. Statistical methods include Pearson's Χ 2 test and Fisher's exact test., Results: Pelvic hemorrhage extended beyond the pelvis to the abdominal area in 47% of the patients, to the thighs in 25% and to the gluteal areas in 81%. The extent of hemorrhage was significantly associated with the need for blood transfusions (p = 0.011) and angiography (p < 0.001), but not with 30-day mortality., Conclusion: Traumatic pelvic bleeding frequently extends beyond the true pelvis. Extrapelvic hemorrhage correlates with an increased need of transfusions, but not with 30-day mortality. Further studies are needed to assess whether present techniques to control pelvic bleeding need to be modified in order to further reduce mortality in traumatic pelvic hemorrhage. Advances in knowledge: The study shows localization of pelvic hemorrhage in trauma patients. It may help to select patients in need of further interventions to control bleeding.

Introduction: Although pelvic fracture urethral injuries (PFUIs) are rare, approximately half these patients will report erectile dysfunction (ED) after their injuries. The anatomic relations of the cavernosal nerves and arteries to the bones of the pelvis and the urethra put these structures at significant risk at the time of PFUI. This review examines the epidemiology, evaluation, and management of ED in this patient population., Aim: To evaluate the epidemiology, pathophysiology, diagnosis, and management of patients with ED after PFUI., Methods: A literature review was performed to identify articles on PubMed published before May 2017 addressing PFUI and ED., Main Outcome Measures: Incidence, mechanisms, risk factors, evaluation, and management strategies of ED after PFUI were analyzed., Results: Patients with pelvic fractures are at risk of post-injury ED, whereas those with PFUI appear to be at even higher risk. Different potential mechanisms contributing to the pathophysiology of ED in this setting have been described in the literature, including damage to the nervous supply to the penis, arterial insufficiency, and veno-occlusive dysfunction. However, there is a lack of consensus on the predominant etiology. Appropriate diagnostic evaluation can help to elucidate the underlying pathophysiology on an individual basis and can help guide management. Oral therapies, intracavernosal injections, and inflatable penile prostheses have shown great success. Furthermore, unlike patients with ED from other causes, select patients with isolated arteriogenic ED are potentially eligible for penile revascularization procedures., Conclusion: Because most patients with pelvic trauma are younger than 40 years with a significant life expectancy, appropriate diagnosis and management of ED after PFUI can greatly improve quality of life and allow resumption of post-injury sexual function. Identification of the causative pathology can help tailor treatment on an individual basis. Johnsen NV, Kaufman MR, Dmochowski RR, Milam DF. Erectile Dysfunction Following Pelvic Fracture Urethral Injury. Sex Med Rev 2018;6;114-123., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual-energy X-ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral-fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

It has been suggested that normalization of bone turnover may improve clinical outcome in Paget's disease of bone (PDB) by preventing complications such as fractures and the development of osteoarthritis. Here we investigated the long-term effects of a treatment strategy that aimed to normalize bone turnover in PDB with that of symptomatic treatment. The study group comprised 502 subjects who were enrolled into a 3-year extension of the Paget's Disease: Randomized Trial of Intensive versus Symptomatic Management (PRISM) study. Intensive bisphosphonate therapy was continued in 270 of these subjects with the aim of normalizing bone turnover using zoledronic acid as the treatment of first choice. Symptomatic treatment continued in 232 subjects in whom bisphosphonates were only given for the treatment of bone pain. The primary outcome was fracture and secondary outcomes were orthopedic procedures, quality of life, and bone pain, adjusted for baseline characteristics. Serum total alkaline phosphatase (ALP) concentrations were significantly lower in the intensive group on entry to the study and the differences between groups increased as the study progressed. There were no clinically important differences in quality of life measures or bone pain between the treatment groups. Intensive treatment was associated with a nonsignificant increase in fracture risk (hazard ratio = 1.90; 95% CI, 0.91 to 3.98; p = 0.087), orthopedic procedures (1.81; 95% CI, 0.71 to 4.61; p = 0.214), and serious adverse events (relative risk 1.28; 95% CI, 0.96 to 1.42). We conclude that long-term intensive bisphosphonate therapy confers no clinical benefit over symptomatic therapy and is associated with a nonsignificant increase in the risk of fractures, orthopedic events, and serious adverse events. The results of this study suggest that in patients with established PDB, bisphosphonate therapy should focus on control of symptoms rather than suppression of bone turnover. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Body composition and muscle function have important implications for falls and fractures in older adults. We aimed to investigate longitudinal associations between sarcopenic obesity and its components with bone mineral density (BMD) and incident falls and fractures in Australian community-dwelling older men. A total of 1486 men aged ≥70 years from the Concord Health and Ageing in Men Project (CHAMP) study were assessed at baseline (2005-2007), 2-year follow-up (2007-2009; n = 1238), and 5-year follow-up (2010-2013; n = 861). At all three time points, measurements included appendicular lean mass (ALM), body fat percentage and total hip BMD, hand-grip strength, and gait speed. Participants were contacted every 4 months for 6.1 ± 2.1 years to ascertain incident falls and fractures, the latter being confirmed by radiographic reports. Sarcopenic obesity was defined using sarcopenia algorithms of the European Working Group on Sarcopenia (EWGSOP) and the Foundation for the National Institutes of Health (FNIH) and total body fat ≥30% of total mass. Sarcopenic obese men did not have significantly different total hip BMD over 5 years compared with non-sarcopenic non-obese men (p > 0.05). EWGSOP-defined sarcopenic obesity at baseline was associated with significantly higher 2-year fall rates (incidence rate ratio [IRR] 1.66; 95% confidence interval [CI] 1.16-2.37), as were non-sarcopenic obesity (1.30; 1.04-1.62) and sarcopenic non-obesity (1.58; 1.14-2.17), compared with non-sarcopenic non-obese. No association with falls was found for sarcopenic obesity using the FNIH definition (1.01; 0.63-1.60), but after multivariable adjustment, the FNIH-defined non-sarcopenic obese group had a reduced hazard for any 6-year fracture compared with sarcopenic obese men (hazard ratio 0.44; 95% CI 0.23-0.86). In older men, EWGSOP-defined sarcopenic obesity is associated with increased fall rates over 2 years, and FNIH-defined sarcopenic obese men have increased fracture risk over 6 years compared with non-sarcopenic obese men. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Chronic obstructive pulmonary disease (COPD) is associated with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and altered microstructure by bone histomorphometry and micro-computed tomography. Nevertheless, not all COPD patients sustain fragility fractures. In the present study, we used Raman microspectroscopic analysis to determine bone compositional properties at actively forming trabecular surfaces (based on double fluorescent labels) in iliac crest biopsies from 19 postmenopausal COPD patients (aged 62.1 ± 7.3 years). Additionally, we analyzed trabecular geometrical centers, representing tissue much older than the forming surfaces. Eight of the patients had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. None of the patients had taken oral glucocorticoids. The monitored parameters were mineral/matrix ratio (MM), nanoporosity, and relative glycosaminoglycan (GAG), lipid, and pyridinoline contents (PYD). There were no significant differences between the glucocorticoid-treated patients and those who did not receive any. On the other hand, COPD patients sustaining fragility fractures had significantly lower nanoporosity and higher MM and PYD values compared with COPD patients without fragility fractures. To the best of our knowledge, this is the first study to discriminate between fracture and non-fracture COPD patients based on differences in the material properties of bone matrix. Given that these bone material compositional differences are evident close to the cement line (a major bone interface), they may contribute to the inferior bone toughness and coupled with the lower lumbar spine bone mineral density values result in the fragility fractures prevalent in these patients. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Osteogenesis imperfecta (OI) is a hereditary, clinically heterogeneous, connective tissue disorder. The population prevalence of OI in Denmark is 10.6 in 100,000. A hallmark of the disease is frequent fractures that are often precipitated by minimal trauma. The aim of the current study was to compare the fracture rates across the lifespan of patients with OI with that of a reference population from the general population. The present study was a Danish nationwide, population-based, cohort study using register data. We identified 644 (55.6% females) patients in the OI cohort through the Danish National Patient Register and 3361 (55.2% females) persons, randomly selected from the Civil Registry System. A total of 416 patients with OI experienced a total of 1566 fractures during the observation period of median 17.9 years (interquartile range [IQR], 12.4 to 18.0 years), summing to 10137 person years. In comparison, 709 persons in the reference population experienced a total of 1018 fractures during follow-up. Both male and female patients with OI had an increased fracture rate throughout their life. The fracture rate ratio for participants aged 0 to 19 years was 10.7, for participants aged 20 to 54 years 17.2, and for participants aged 55 years and over 4.1 when compared to the reference population. The highest fracture rate was seen in males with OI aged 0 to 19 years (257 fractures per 1000 person-years). The fractures appear to follow the same pattern as in the general population, with a peak during the toddler and adolescent years (incidence rate [IR] 233.9 per 1000 person years), fewer fractures during adulthood (IR 84.5 per 1000 person years), and increased fracture rates in older women (IR 111.9 per 1000 person years). This is the largest register-based nationwide study on the fracture epidemiology of patients with OI. The risk of fractures seems largest in the childhood and adolescent years, and the relative risk of fracture declines with age in patients with OI compared to the general population. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Standard DXA measurements, including Fracture Risk Assessment Tool (FRAX) scores, have shown limitations in assessing fracture risk in Type 2 Diabetes (T2D), underscoring the need for novel biomarkers and suggesting that other pathomechanisms may drive diabetic bone fragility. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues proportional to local disease severity and were recently found to be crucial to bone homeostasis and T2D. Here, we studied, if and which circulating miRNAs or combinations of miRNAs can discriminate best fracture status in a well-characterized study of diabetic bone disease and postmenopausal osteoporosis (n = 80 postmenopausal women). We then tested the most discriminative and most frequent miRNAs in vitro. Using miRNA-qPCR-arrays, we showed that 48 miRNAs can differentiate fracture status in T2D women and that several combinations of four miRNAs can discriminate diabetes-related fractures with high specificity and sensitivity (area under the receiver-operating characteristic curve values [AUCs], 0.92 to 0.96; 95% CI, 0.88 to 0.98). For the osteoporotic study arm, 23 miRNAs were fracture-indicative and potential combinations of four miRNAs showed AUCs from 0.97 to 1.00 (95% CI, 0.93 to 1.00). Because a role in bone homeostasis for those miRNAs that were most discriminative and most present among all miRNA combinations had not been described, we performed in vitro functional studies in human adipose tissue-derived mesenchymal stem cells to investigate the effect of miR-550a-5p, miR-188-3p, and miR-382-3p on osteogenesis, adipogenesis, and cell proliferation. We found that miR-382-3p significantly enhanced osteogenic differentiation (p < 0.001), whereas miR-550a-5p inhibited this process (p < 0.001). Both miRNAs, miR-382-3p and miR-550a-5p, impaired adipogenic differentiation, whereas miR-188-3p did not exert an effect on adipogenesis. None of the miRNAs affected significantly cell proliferation. Our data suggest for the first time that miRNAs are linked to fragility fractures in T2D postmenopausal women and should be further investigated for their diagnostic potential and their detailed function in diabetic bone. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

This study aimed to examine progressive temporal relationships between changes in major reproductive hormones across three waves of a cohort study of older men and (1) changes in bone mineral density (BMD) and (2) incident fractures (any, hip or non-vertebral) over an average of 6 years of follow-up. The CHAMP cohort of men aged 70 years and older were assessed at baseline (2005 to 2007, n = 1705), 2-year follow-up (n = 1367), and 5-year follow-up (n = 958). Serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) (by liquid chromatography-tandem mass spectrometry [LC-MS/MS]), and sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (by immunoassay) were measured at all time-points, whereas free testosterone (cFT) was calculated using a well-validated formula. Hip BMD was measured by dual-energy X-ray absorptiometry (DXA) at all three time-points, and fracture data were verified radiographically. Statistical modeling was done using general estimating equations (GEEs). For total hip BMD, univariable analyses revealed inverse associations with temporal changes in serum SHBG, FSH, and LH and positive associations for serum E1 and cFT across the three time-points. In models adjusted for multiple covariables, serum SHBG (β = -0.029), FSH (β = -0.065), LH (β = -0.049), E1 (β = 0.019), and cFT (β = 0.033) remained significantly associated with hip BMD. However for femoral neck BMD, only FSH (β = -0.048) and LH (β = -0.036) remained associated in multivariable-adjusted models. Temporal change in serum SHBG, but not T, E2, or other hormonal variables, was significantly associated with any, nonvertebral or hip fracture incidence in univariable analyses. In multivariable-adjusted models, temporal increase in serum SHBG over time remained associated with any fracture (β = 0.060) and hip fracture (β = 0.041) incidence, but not nonvertebral fracture incidence. These data indicate that a progressive increase in circulating SHBG over time predicts bone loss and fracture risk in older men. Further studies are warranted to further characterize changes in circulating SHBG as a mechanism and/or biomarker of bone health during male ageing. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Introduction: good oral hygiene is important for eating, talking and improved quality of life, and is part of basic patient care, but there are few observational studies in hospitalised older patients. The aim of this study is to investigate dental plaque load in older patients over time in hospital., Methods: we examined the mouths of 93 patients with lower limb fracture prospectively at day 1, 7 and 14 after admission in a Newcastle upon Tyne Hospital. We assessed dental and denture plaque load, dry mouth symptoms and tooth number, along with demographic and frailty variables. We used univariate generalised linear modelling and mixed effects models to investigate associations between increased plaque and patient characteristics., Results: in dentate patients, plaque score increased with time in hospital (P = 0.007, odds ratio (OR): 1.02; 95% confidence of interval (CI): 1.01-1.04). Frailty (P = 0.015, OR: 1.19; 95% CI: 1.04-1.37), dementia (P < 0.001, OR: 4.30; 95% CI: 2.03-9.12), residence in an institution (P < 0.001, OR: 4.61; 95% CI: 2.18-9.74), decreased mobility (P = 0.013, OR: 0.97; 95% CI: 0.96-0.99), but not Charlson comorbidity index (P = 0.102, OR: 1.08; 95% CI: 0.99-1.19), were associated with increased plaque scores at every time point., Conclusions: oral hygiene deteriorated in dentate patients in hospital. Plaque scores were significantly higher in patients who were more likely to be dependent on others for their oral hygiene., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Context: Cerebral palsy (CP) increases fracture risk through diminished ambulation, nutritional deficiencies, and anticonvulsant medication use. Studies examining bone mineral density (BMD) in adults with CP are limited., Objective: To examine the relationship between body composition, BMD, and fractures in adults with CP. The effect of functional, nutritional, and endocrine factors on BMD and body composition is also explored., Design: Retrospective cross-sectional study., Setting and Participants: Forty-five adults with CP (mean age, 28.3 ± 11.0 years) who had dual-energy x-ray absorptiometry imaging at a single tertiary hospital between 2005 and 2015., Results: Seventeen (38%) had a past history of fragility fracture; 43% had a Z-score of ≤ -2.0 at the lumbar spine (LS) and 41% at the femoral neck (FN). In nonambulatory patients, every one unit decrease in FN Z-score increased the risk of fracture 3.2-fold (95% confidence interval, 1.07-9.70; P = .044). Stepwise linear regression revealed that the Gross Motor Function Classification System was the best predictor of LS Z-score (R(2) = 0.550; β = -0.582; P = .002) and FN Z-score (R(2) = 0.428; β = -0.494; P = .004); 35.7% of the variance in BMD was accounted for by lean tissue mass. Hypogonadism, present in 20% of patients, was associated with reduced lean tissue mass and reduced LS BMD. Lean tissue mass positively correlated with BMD in eugonadal patients, but not in hypogonadal patients., Conclusions: Low BMD and fractures are common in adults with CP. This is the first study to document hypogonadism in adults with CP with detrimental changes in body composition and BMD.

Nonsurgical hypoparathyroidism (HypoPT) is a rare disorder most often caused by mutations in different genes. It is characterized by hypocalcaemia with inappropriately low PTH levels. Knowledge about this group of patients, including their mortality and morbidity, is very sparse. The aim was to identify all patients diagnosed with nonsurgical HypoPT in Denmark and assess their mortality and risk of complications. Through registers and review of individual patient hospital charts we identified all patients diagnosed with nonsurgical HypoPT in Denmark between 1977 and 2012. We assessed their mortality and morbidity by comparing them with a group of age- and gender-matched population-based controls. We identified a total of 180 patients with nonsurgical HypoPT among whom 123 (68%) were alive at the date of follow-up (prevalence of 2.3/100,000 inhabitants). Compared with controls, mortality was not increased, but patients had a significantly increased risk of renal insufficiency (hazard ratio [HR] 6.01), cardiovascular diseases (HR 1.91), neuropsychiatric complications (HR 2.45), infections (HR 1.94), seizures (HR 10.05), cataract (HR 4.21), and fractures at the upper extremities (HR 1.93). In contrast patients had significantly reduced risk of malignant diseases (HR 0.44). In conclusion, nonsurgical HypoPT is a rare disease associated with a number of complications that should be considered when taking care of these patients., (© 2015 American Society for Bone and Mineral Research.)

Hypophosphatasia is an inborn error of metabolism caused by mutations in the ALPL gene. It is characterized by low serum alkaline phosphatase (ALP) activity and defective mineralization of bone, but the phenotype varies greatly in severity depending on the degree of residual enzyme activity. We describe a man with compound heterozygous mutations in ALPL, but no previous bone disease, who suffered numerous disabling fractures after he developed progressive renal failure (for which he eventually needed dialysis treatment) and was prescribed alendronate treatment. A bone biopsy showed marked osteomalacia with low osteoblast numbers and greatly elevated pyrophosphate concentrations at mineralizing surfaces. In vitro testing showed that one mutation, T117H, produced an ALP protein with almost no enzyme activity; the second, G438S, produced a protein with normal activity, but its activity was inhibited by raising the media phosphate concentration, suggesting that phosphate retention (attributable to uremia) could have contributed to the phenotypic change, although a pathogenic effect of bisphosphonate treatment is also likely. Alendronate treatment was discontinued and, while a suitable kidney donor was sought, the patient was treated for 6 months with teriparatide, which significantly reduced the osteomalacia. Eighteen months after successful renal transplantation, the patient was free of symptoms and the scintigraphic bone lesions had resolved. A third bone biopsy showed marked hyperosteoidosis but with plentiful new bone formation and a normal bone formation rate. This case illustrates how pharmacological (bisphosphonate treatment) and physiologic (renal failure) changes in the "environment" can dramatically affect the phenotype of a genetic disorder., (© 2015 American Society for Bone and Mineral Research.)

Context: The significance of studies suggesting an increased risk of bone fragility fractures with hyponatremia through mechanisms of induced bone loss and increased falls has not been demonstrated in large patient populations with different types of hyponatremia., Objective: This matched case-control study evaluated the effect of hyponatremia on osteoporosis and fragility fractures in a patient population of more than 2.9 million., Design, Setting, and Participants: Osteoporosis (n = 30 517) and fragility fracture (n = 46 256) cases from the MedStar Health database were matched on age, sex, race, and patient record length with controls without osteoporosis (n = 30 517) and without fragility fractures (n = 46 256), respectively. Cases without matched controls or serum sodium (Na(+)) data or with Na(+) with a same-day blood glucose greater than 200 mg/dL were excluded., Main Outcome Measures: Incidence of diagnosis of osteoporosis and fragility fractures of the upper or lower extremity, pelvis, and vertebrae were the outcome measures., Results: Multivariate conditional logistic regression models demonstrated that hyponatremia was associated with osteoporosis and/or fragility fractures, including chronic [osteoporosis: odds ratio (OR) 3.97, 95% confidence interval (CI) 3.59-4.39; fracture: OR 4.61, 95% CI 4.15-5.11], recent (osteoporosis: OR 3.06, 95% CI 2.81-3.33; fracture: OR 3.05, 95% CI 2.83-3.29), and combined chronic and recent hyponatremia (osteoporosis: OR 12.09, 95% CI 9.34-15.66; fracture: OR 11.21, 95% CI 8.81-14.26). Odds of osteoporosis or fragility fracture increased incrementally with categorical decrease in median serum Na(+)., Conclusions: These analyses support the hypothesis that hyponatremia is a risk factor for osteoporosis and fracture. Additional studies are required to evaluate whether correction of hyponatremia will improve patient outcomes.

Context: Osteoporosis is often a presenting sign of celiac disease (CD). Whether skeletal fragility in CD is associated with microarchitectural abnormalities is not known., Objective: The objective of the study was to evaluate microarchitecture and biomechanical properties of bone in CD., Design: This was a case-control study., Setting: The study was conducted at a university hospital outpatient facility., Patients: Patients included premenopausal women with newly diagnosed CD (n = 33) and healthy controls (n = 33)., Main Outcome Measures: Areal bone mineral density by dual-energy x-ray absorptiometry was measured as was trabecular and cortical volumetric bone mineral density (vBMD) and microarchitecture by high-resolution peripheral computed tomography of the distal radius and tibia. Whole-bone stiffness estimated by finite element analysis. PTH, 25-hydroxyvitamin D, and bone turnover markers were also measured., Results: Groups had similar age, race, and body mass index. Both groups had sufficient 25-hydroxyvitamin D and normal calcium and PTH. Areal bone mineral density was lower in CD. By high-resolution peripheral computed tomography, CD had lower trabecular vBMD, fewer, more widely, and irregularly spaced trabeculae at both the radius and tibia (8%-33%). At the tibia, they also had lower total density (8%) and thinner cortices (10%). Whole-bone stiffness and failure load were lower (11%-21%) in CD at both sites. Biomechanical deficits were associated with trabecular abnormalities., Conclusions: Women with CD had abnormal vBMD and microarchitecture at both the radius and tibia. Trabecular bone was preferentially affected. These deficits were associated with lower estimates of skeletal strength. These findings suggest a potential structural mechanism for skeletal fragility in CD and support further research into the pathogenesis of fracture in this population.

Fractures are common in chronic kidney disease (CKD). The optimal methods by which to assess fracture risk are unknown, in part, due to a lack of prospective studies. We determined if bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and/or high-resolution peripheral quantitative computed tomography (HRpQCT) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD. BMD was measured by DXA (at the total hip, lumbar spine, ultradistal, and 1/3 radius) and by HRpQCT (at the radius), and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures. The mean age of the subjects was 62 years with equal numbers having stages 3, 4, and 5 CKD. Over 2 years there were 51 fractures in 35 subjects. BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without. For example, the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 (95% confidence interval [CI], 0.73 to 0.80) and in those without fracture was 0.95 g/cm2 (95% CI, 0.92 to 0.98). Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without. For example, volumetric BMD in those with incident fractures was 232 mg HA/cm3 (95% CI, 213 to 251) and in those without fracture was 317.6 mg HA/cm3 (95% CI, 306 to 329.1). Bone loss occurred in all subjects, but was significantly greater among those with incident fractures. Our data demonstrate that low BMD (by DXA and HRpQCT) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD., (© 2014 American Society for Bone and Mineral Research.)

Bisphosphonates are widely used off-label in the treatment of patients with osteogenesis imperfecta (OI) with the intention of reducing the risk of fracture. Although there is strong evidence that bisphosphonates increase bone mineral density in osteogenesis imperfecta, the effects on fracture occurrence have been inconsistent. The aim of this study was to gain a better insight into the effects of bisphosphonate therapy on fracture risk in patients with osteogenesis imperfecta by conducting a meta-analysis of randomized controlled trials in which fractures were a reported endpoint. We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials in which the effects of bisphosphonates on fracture risk in osteogenesis imperfecta were compared with placebo and conducted a meta-analysis of these studies using standard methods. Heterogeneity was assessed using the I2 statistic. Six eligible studies were identified involving 424 subjects with 751 patient-years of follow-up. The proportion of patients who experienced a fracture was not significantly reduced by bisphosphonate therapy (Relative Risk [RR] = 0.83 [95% confidence interval 0.69-1.01], p = 0.06) with no heterogeneity between studies (I2  = 0). The fracture rate was reduced by bisphosphonate treatment when all studies were considered (RR = 0.71 [0.52-0.96], p = 0.02), but with considerable heterogeneity (I2  = 36%) explained by one study where a small number of patients in the placebo group experienced a large number of fractures. When this study was excluded, the effects of bisphosphonates on fracture rate was not significant (RR = 0.79 [0.61-1.02], p = 0.07, I2  = 0%). We conclude that the effects of bisphosphonates on fracture prevention in osteogenesis imperfecta are inconclusive. Adequately powered trials with a fracture endpoint are needed to further investigate the risks and benefits of bisphosphonates in this condition., (© 2014 American Society for Bone and Mineral Research.)

Half of fragility fractures occur in individuals with nonosteoporotic BMD (BMD T-score > -2.5); however, there is no information on postfracture adverse events of subsequent fracture and mortality for different BMD levels. The objective of this work was to determine the risk and predictors of subsequent fracture and excess mortality following initial fracture according to BMD. The subjects were community-dwelling participants aged 60+ years from the Dubbo Osteoporosis Epidemiology Study with incident fractures followed from 1989 to 2011. The outcome measurements were as follows: risk of subsequent fracture and mortality according to BMD categorized as normal (T-score < -1), osteopenia (T-score ≤ -1 and > -2.5), and osteoporosis (T-score ≤ -2.5). There were 528 low-trauma fractures in women and 187 in men. Of these, 12% occurred in individuals with normal BMD (38 women, 50 men) and 42% in individuals with osteopenia (221 women, 76 men). The relative risk (RR) of subsequent fracture was >2.0-fold for all levels of BMD (normal BMD: 2.0 [1.2 to 3.3] for women and 2.1 [1.2 to 3.8] for men; osteopenia: 2.1 [1.7 to 2.6] for women and 2.5 [1.6 to 4.1] for men; and osteoporosis 3.2 [2.7 to 3.9] for women and 2.1 [1.4 to 3.1] for men. The likelihood of falling and reduced quadriceps strength contributed to subsequent fracture risk in women with normal BMD. By contrast with subsequent fracture risk, postfracture mortality was increased particularly in individuals with low BMD (age-adjusted standardized mortality ratio [SMR] for osteopenia 1.3 [1.1 to 1.7] and 2.2 [1.7 to 2.9] for women and men, respectively, and osteoporosis 1.7 [1.5 to 2.0] and 2.7 [2.0 to 3.6] for women and men, respectively). This study demonstrates the high burden of subsequent fracture in individuals with normal BMD and osteopenia, and excess mortality particularly for those with osteopenia (and osteoporosis). These findings highlight the importance of these fractures and underscore the gap in evidence for benefit of antiosteoporotic treatment for fragility fracture, in those with only mildly low BMD., (© 2014 American Society for Bone and Mineral Research.)

Objectives: Pelvic fractures are markers of severe injury and are often associated with lower genitourinary injuries. The purpose of this study was to investigate the incidence of lower genitourinary injuries and complaints associated with pelvic fractures sustained in combat among nonsurvivors and survivors., Methods: The Armed Forces Medical Examiner System and The Joint Theater Trauma Registry databases were searched to identify survivors and nonsurvivors who sustained a pelvic fracture in combat in 2008. Survivor and autopsy data consisted of injury mode and mechanism and associated organ and extremity injuries. Pelvic fractures were classified using the Tile system., Results: The database search yielded 91 nonsurvivors and 10 survivors with pelvic fractures. Forty-one patients (40%) sustained 61 genitourinary injuries. The majority of genitourinary injuries in nonsurvivors were associated with Tile C pelvic fractures (70%). Twenty percent of survivors had genitourinary injuries, all of which were associated with Tile A fractures., Conclusions: A higher incidence of genitourinary injuries in patients with combat-related pelvic fractures (60%) was found than that of their civilian counterparts. Of the survivors, 100% of those with genitourinary injuries were being treated for erectile dysfunction at their last follow-up. Continued collaboration between orthopaedic surgeons and urologist is needed to address these concurrent injuries., (Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.)

Paget's disease of bone (PDB) is the second most common bone disease mostly developing after 50 years of age at one or more localized skeletal sites; it is associated with severely high bone turnover, bone enlargement, bowing/deformity, cracking, and pain. Here, to specifically address the origins of the deteriorated mechanical integrity, we use a cohort of control and PDB human biopsies to investigate multiscale architectural and compositional modifications to the bone structure (ie, bone quality) and relate these changes to mechanical property measurements to provide further insight into the clinical manifestations (ie, deformities and bowing) and fracture risk caused by PDB. Here, at the level of the collagen and mineral (ie, nanometer-length scale), we find a 19% lower mineral content and lower carbonate-to-phosphate ratio in PDB, which accounts for the 14% lower stiffness and 19% lower hardness promoting plastic deformation in pathological bone. At the microstructural scale, trabecular regions are known to become densified, whereas cortical bone loses its characteristic parallel-aligned osteonal pattern, which is replaced with a mosaic of lamellar and woven bone. Although we find this loss of anisotropic alignment produces a straighter crack path in mechanically-loaded PDB cases, cortical fracture toughness appears to be maintained due to increased plastic deformation. Clearly, the altered quality of the bone structure in PDB affects the mechanical integrity leading to complications such as bowing, deformities, and stable cracks called fissure fractures associated with this disease. Although the lower mineralization and loss of aligned Haversian structures do produce a lower modulus tissue, which is susceptible to deformities, our results indicate that the higher levels of plasticity may compensate for the lost microstructural features and maintain the resistance to crack growth., (© 2014 American Society for Bone and Mineral Research.)

Diverging international trends in fracture rates have been observed, with most reports showing that fracture rates have stabilized or decreased in North American and many European populations. We studied two complementary population-based historical cohorts from the Province of Manitoba, Canada (1996-2006) to determine whether declining osteoporotic fracture rates in Canada are attributable to trends in obesity, osteoporosis treatment, or bone mineral density (BMD). The Population Fracture Registry included women aged 50 years and older with major osteoporotic fractures, and was used to assess impact of changes in osteoporosis treatment. The BMD Registry included all women aged 50 years and older undergoing BMD tests, and was used to assess impact of changes in obesity and BMD. Model-based estimates of temporal changes in fracture rates (Fracture Registry) were calculated. Temporal changes in obesity and BMD and their association with fracture rates (BMD Registry) were estimated. In the Fracture Registry (n=27,341), fracture rates declined 1.6% per year (95% confidence interval [CI], 1.3% to 2.0%). Although osteoporosis treatment increased from 5.6% to 17.4%, the decline in fractures was independent of osteoporosis treatment. In the BMD Registry (n=36,587), obesity increased from 12.7% to 27.4%. Femoral neck BMD increased 0.52% per year and lumbar spine BMD increased 0.32% per year after covariate adjustment (p<0.001). Major osteoporotic fracture rates decreased in models that did not include femoral neck BMD (fully adjusted annual change -1.8%; 95% CI, -2.9 to -0.5), but adjusting for femoral neck BMD accounted for the observed reduction (annual change -0.5%; 95% CI, -1.8 to +1.0). In summary, major osteoporotic fracture rates declined substantially and linearly from 1996 to 2006, and this was explained by improvements in BMD rather than greater rates of obesity or osteoporosis treatment., (© 2014 American Society for Bone and Mineral Research.)

Acute kidney injury (AKI) has a negative impact on long-term renal function and prognosis. However, the association between acute renal dysfunction and long-term effects on bone disorders has not yet been characterized. Using a population-based cohort study, we aimed to evaluate associations between AKI and long-term effects on bone fractures. We identified relevant data of all hospitalized patients aged >18 years with histories of dialysis-requiring AKI, with subsequent recovery and discharge, from the claim records of the Taiwan National Health Insurance database between 2000 and 2008. We determined long-term de novo bone fracture and all-cause mortality after patients' index-hospitalization discharge using propensity score-adjusted Cox proportional hazard model. Varying-time models were used to adjust for long-term effects of end-stage renal disease (ESRD) on main outcomes. Among 448 AKI patients who had dialysis and survived 90 days after index-hospitalization discharge without reentering dialysis, 273 were male (60.9%) with a mean age of 61.4 ± 16.6 years. Controls included 1792 hospitalized patients without AKI, dialysis, or bone fracture history. In the AKI recovery group, bone fracture incidence was 320 per 10,000 person-years and hazard ratio (HR) of long-term bone fracture was 1.25 (p = 0.049) compared with the control group, independent of subsequent ESRD status (HR = 1.55; p = 0.01). Both AKI recovery status (HR = 2.31; p < 0.001) and time varying factor of bone fracture (HR = 1.43; p < 0.001) were independent predictors of mortality compared with controls. In conclusion, AKI requiring temporary dialysis independently increases long-term risk of bone fracture, regardless of subsequent progression to ESRD. Long-term bone fractures may negatively impact patient mortality., (© 2014 American Society for Bone and Mineral Research.)

Context: Hypophosphatasia (HPP) features deficient activity of the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP) due to loss-of-function mutation(s) within the TNSALP gene. Consequently, inorganic pyrophosphate, a TNSALP substrate and inhibitor of mineralization, accumulates extracellularly. This can cause rickets or osteomalacia., Objective: We report a 55-year-old man with HPP and chronic renal failure (CRF) requiring hemodialysis who developed severe hypercalcemia acutely after traumatic fractures and immobilization. He manifested HPP in childhood and in middle age received hemodialysis for CRF attributed to hypertension and anti-inflammatory medication. He took 2 g of calcium carbonate orally each day to bind dietary phosphorus, but never aluminum hydroxide or any form of vitamin D. Pretrauma serum levels of calcium spanned 8.4-10.7 mg/dL (normal [Nl], 8.6-10.3), inorganic phosphate 5.8-6.4 mg/dL (Nl, 2.5-4.5), and PTH 63-75 pg/mL (Nl, 10-55)., Results: Rapid succession falls fractured multiple major bones. Six hours later, he became confused. Serum calcium was 14.9 mg/dL, ionized calcium was 7.4 mg/dL (Nl, 4.5-5.1), and PTH was 16 pg/mL. Hemodialysis quickly corrected his hypercalcemia and confusion. Low serum alkaline phosphatase persisted, and follow-up skeletal histopathology showed that his osteomalacia was severe., Conclusion: Hemodialysis does not heal the skeletal disease of HPP. During sudden fracture immobilization in HPP, sufficient calcium can emerge from bone, perhaps from a rapidly exchangeable calcium pool, to cause acute severe hypercalcemia if the kidneys cannot compensate for the mineral efflux. Hence, we worry that acute hypercalcemia might accompany sudden immobilization in CRF patients without HPP if they have adynamic bone disease.

This study assessed the ability of multisite quantitative ultrasound (mQUS) to predict fracture over a 5-year follow-up. Participants were a subset of the Canadian Multicentre Osteoporosis Study. mQUS-assessed speed of sound (SOS in m/s) at three sites (distal radius, tibia, and phalanx) and extensive questionnaires were completed, after which participants were followed for 5 years and incident fractures recorded. Two survival analyses were completed for each site--a univariate analysis and an adjusted multivariate analysis controlling for age, antiresorptive use, femoral neck bone mineral density, number of diseases, previous fractures, body mass index (BMI), parental history of hip fracture, current smoking, current alcoholic drinks >3 per day, current use of glucocorticoids, and rheumatoid arthritis diagnosis (variables from the FRAX 10-year fracture risk assessment tool). The unit of change for regression analyses was one standard deviation for all measurement sites, specific to site and sex. Separate analyses were completed for all clinical fractures, nonvertebral fractures, and hip fractures by sex. There were 2633 women and 1108 men included, and they experienced 204 incident fractures over 5 years (5.5% fractured). Univariate models revealed statistically significant (p < 0.05) predictive ability of mQUS for all three measurement sites for women alone for all three fracture types (one standard deviation decrease in SOS was associated with a 52% to 130% increase in the risk of fracture), but not for the men's group. The adjusted model found that measures at the distal radius and tibia in the women's group could significantly (p < 0.05) predict all clinical fractures and nonvertebral fractures within the next 5 years (one standard deviation decrease in SOS was associated with a 25% to 31% increase in the risk of fracture). mQUS provided significant 5-year clinical fracture prediction in women, independent of bone mineral density and other significant risk factors for fracture, when measured at the distal radius and tibia sites., (Copyright © 2013 American Society for Bone and Mineral Research.)

A site-dependent association between obesity and fracture has been reported in postmenopausal women. In this study we investigated the relationship between body mass index (BMI) and fracture at different skeletal sites in older men (≥65 years). We carried out a population-based cohort study using data from the Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP(Q) ) database. SIDIAP(Q) contains the primary care and hospital admission computerized medical records of >1300 general practitioners (GPs) in Catalonia (Northeast Spain), with information on a representative 30% of the population (>2 million people). In 2007, 186,171 men ≥65 years were eligible, of whom 139,419 (74.9%) had an available BMI measurement. For this analysis men were categorized as underweight/normal (BMI < 25 kg/m(2) , n = 26,298), overweight (25 ≤ BMI < 30 kg/m(2) , n = 70,851), and obese (BMI ≥ 30 kg/m(2) , n = 42,270). Incident fractures in the period 2007 to 2009 were ascertained using International Classification of Diseases, 10th edition (ICD-10) codes. A statistically significant reduction in clinical spine and hip fractures was observed in obese (relative risk [RR], 0.65; 95% confidence interval [CI], 0.53-0.80 and RR, 0.63; 95% CI, 0.54-0.74, respectively), and overweight men (RR, 0.77; 95% CI, 0.64-0.92 and RR, 0.63; 95% CI 0.55-0.72, respectively) when compared with underweight/normal men. Additionally, obese men had significantly fewer wrist/forearm (RR, 0.77; 95% CI, 0.61-0.97) and pelvic (RR, 0.44; 95% CI, 0.28-0.70) fractures than underweight/normal men. Conversely, multiple rib fractures were more frequent in overweight (RR, 3.42; 95% CI, 1.03-11.37) and obese (RR, 3.96; 95% CI, 1.16-13.52) men. In this population-based cohort of older men, obesity was associated with a reduced risk of clinical spine, hip, pelvis, and wrist/forearm fracture and increased risk of multiple rib fractures when compared to normal or underweight men. Further work is needed to identify the mechanisms underlying these associations., (Copyright © 2013 American Society for Bone and Mineral Research.)

Subjects with inflammatory bowel disease (IBD) are at increased risk for hip and other major osteoporotic fractures. However, previous analyses have not fully accounted for differences in bone mineral density (BMD) and other clinical factors that affect the risk of fracture. The World Health Organization Fracture Risk Assessment tool (FRAX) can be used to predict the 10-year fracture risk from BMD and clinical risk factors. A population-based database containing clinical information on all IBD subjects in the province of Manitoba, Canada, was linked with the Manitoba Bone Mineral Density Database, which contains results of all dual X-ray absorptiometry (DXA) scans in the province. FRAX probabilities were calculated for all subjects aged 50 years or more undergoing baseline DXA testing. Subjects were followed for occurrence of major osteoporotic fractures (MOF; hip, clinical spine, wrist, humerus). Cox proportional hazards models were used to determine whether IBD was independently predictive of MOF or hip fracture. After controlling for FRAX fracture probability computed with BMD, IBD was not associated with a significantly increased risk for MOF (hazard ratio [HR] = 1.12, 95% confidence interval [CI], 0.83-1.55) but was associated with an increased risk for hip fracture (HR = 2.14; 95% CI, 1.26-3.65). The addition of femoral neck T-score to FRAX probability without knowledge of BMD had a negligible effect on the estimated HRs for IBD, suggesting that IBD mediates any effect on fracture risk independently of femoral neck BMD. After controlling for FRAX probability, subjects with IBD are not at an increased risk for overall MOF, but may be at increased risk of hip fracture., (Copyright © 2013 American Society for Bone and Mineral Research.)

The primary goal of this study was to assess peripheral bone microarchitecture and strength in postmenopausal women with type 2 diabetes with fragility fractures (DMFx) and to compare them with postmenopausal women with type 2 diabetics without fractures (DM). Secondary goals were to assess differences in nondiabetic postmenopausal women with fragility fractures (Fx) and nondiabetic postmenopausal women without fragility fractures (Co), and in DM and Co women. Eighty women (mean age 61.3 ± 5.7 years) were recruited into these four groups (DMFx, DM, Fx, and Co; n = 20 per group). Participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density and cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro-finite element analysis (µFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p = 0.009; +95.4%, p = 0.020), relative porosity (+58.1%, p = 0.005; +87.9%, p = 0.011) and endocortical bone surface (+10.9%, p = 0.031; +11.5%, p = 0.019) than DM. At the distal radius DMFx had 4.7-fold greater relative porosity (p < 0.0001) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p = 0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius: +36.8%, p = 0.035), and lower total and cortical BMD (ultradistal tibia: -12.6%, p = 0.031; -6.8%, p = 0.011) than DM. DMFx exhibited significantly higher pore-related deficits in stiffness, failure load, and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing nondiabetic Fx and Co, we only found a nonsignificant trend with increase in pore volume (+38.9%, p = 0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women., (Copyright © 2013 American Society for Bone and Mineral Research.)

Background: The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I-III) breast cancer., Materials and Methods: We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes., Results: Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70-1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio [OR], 0.94; 95% CI, 0.64-1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63-0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%., Conclusion: Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment.

Complex Regional Pain Syndrome (CRPS) can result from trauma or after surgery. It is often difficult to manage effectively. If not recognized early, it can result in significant debilitation. Symptoms attributed to CRPS include neuropathic pain, allodynia, sudomotor changes, and decreased range of motion. It can occur with (Type II) or without (Type I) nerve injury. A number of soldiers sustaining extremity injuries during combat have manifested these symptoms. Two subjects were diagnosed with CRPS after sustaining upper extremity injuries during military operations. After failing conservative treatment, Chinese Scalp Acupuncture (CSA) was used once to twice a week for 1 to 4 weeks. CSA resulted in improvement in the pain visual analog scale or numeric rating scale by over 80% in two soldiers with upper extremity CRPS. Additionally, decreased sensory changes and improved function were noted on exam and therapy assessments. Notably, the pain reduction, functional improvement, and normalization of sensation have been fully maintained between treatments. The treatment response had been sustained at 20-month follow-up with no recurrence. CSA provided lasting pain reduction, and improved function and sensation in this group of combatants with upper extremity CRPS.

The purposes of this study were to examine fracture risk profiles at specific bone sites, and to understand why model discrimination using clinical risk factors is generally better in hip fracture models than in models that combine hip with other bones. Using 3-year data from the GLOW study (54,229 women with more than 4400 total fractures), we present Cox regression model results for 10 individual fracture sites, for both any and first-time fracture, among women aged ≥55 years. Advanced age is the strongest risk factor in hip (hazard ratio [HR] = 2.3 per 10-year increase), pelvis (HR = 1.8), upper leg (HR = 1.8), and clavicle (HR = 1.7) models. Age has a weaker association with wrist (HR = 1.1), rib (HR = 1.2), lower leg (not statistically significant), and ankle (HR = 0.81) fractures. Greater weight is associated with reduced risk for hip, pelvis, spine, and wrist, but higher risk for first lower leg and ankle fractures. Prior fracture of the same bone, although significant in nine of 10 models, is most strongly associated with spine (HR = 6.6) and rib (HR = 4.8) fractures. Past falls are important in all but spine models. Model c indices are ≥0.71 for hip, pelvis, upper leg, spine, clavicle, and rib, but ≤0.66 for upper arm/shoulder, lower leg, wrist, and ankle fractures. The c index for combining hip, spine, upper arm, and wrist (major fracture) is 0.67. First-time fracture models have c indices ranging from 0.59 for wrist to 0.78 for hip and pelvis. The c index for first-time major fracture is 0.63. In conclusion, substantial differences in risk profiles exist among the 10 bones considered., (Copyright © 2012 American Society for Bone and Mineral Research.)

There is a dearth of information about the burden of osteoporosis in Canadian men. To fill this gap, we conducted a burden of illness study aimed at estimating the economic burden attributable to osteoporosis in Canadian men aged 50 years and older. Five national data sources were used to estimate health care resource utilization and costs (in 2010 Canadian dollars) associated with osteoporosis in men. Any information gap was supplemented by using data from provincial and community sources. Direct medical costs included costs associated with hospitalizations, same day surgeries, emergency room visits, rehabilitation, chronic care, long-term care, home care, physician visits, and prescribed medications. The value of lost productivity from patients and informal caregivers was also determined to provide a societal perspective. Sensitivity analyses were conducted to evaluate the impact of key assumptions on the results. In fiscal year 2007/2008, the total economic burden of treating and rehabilitating male osteoporotic fractures was estimated at $570 million per year, where direct medical costs accounted for 86%. Acute care utilization was responsible for 70% of all direct costs. About 51% of all hospitalizations were for hip fractures and hip fractures alone accounted for 54% of the acute care spending. If a proportion of Canadian men were assumed to live in long-term care facilities due to osteoporosis, the overall annual cost of osteoporosis would increase from $570 million to $910 million. Male osteoporosis has a substantial economic burden on the Canadian society., Competing Interests: None., (Copyright © 2012 American Society for Bone and Mineral Research.)