Underlying Bone Disease Research Articles

Practical Considerations for the Design, Execution, and Interpretation of Studies Involving Whole-Bone Bending Tests of Rodent Bones.

Skeletal fragility leading to fracture is an American public health crisis resulting in 1.5 million fractures each year and $18 billion in direct care costs. The ability to understand the mechanisms underlying bone disease and the response to treatment is not only desired, but critical. Mechanical testing of bone serves as a valuable technique for understanding and quantifying a bone's susceptibility to fracture. While this method appears simple to perform, inappropriate and inaccurate conclusions may be reached if governing assumptions and key steps are disregarded by the user. This has been observed across disciplines as studies continue to be published with misuse of methods and incorrect interpretation of results. This protocol will serve as a primer for the principles associated with mechanical testing along with the application of these techniques-from considerations of sample size through tissue harvesting and storage, to data analysis and interpretation. With this in hand, valuable information regarding a bone's susceptibility to fracture may be obtained, furthering understanding for both academic research and clinical solutions.

Celiac disease and bone.

Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy.

Drive Time and Receipt of Guideline-Recommended Screening, Diagnosis, and Treatment

Many patients do not receive recommended services. Drive time to health care services may affect receipt of guideline-recommended care, but this has not been comprehensively studied. To assess associations between drive time to care and receipt of guideline-recommended screening, diagnosis, and treatment interventions. This cohort study used administrative data from the National Veterans Health Administration (VA) data merged with Medicare data. Eligible participants were patients using VA services between January 2016 and December 2019. Women ages 65 years or older without underlying bone disease were assessed for osteoporosis screening. Patients with new diagnosis of chronic obstructive pulmonary disease (COPD) indicated by at least 2 encounter codes for COPD or at least 1 COPD-related hospitalization were assessed for receipt of diagnostic spirometry. Patients hospitalized for ischemic heart disease were assessed for cardiac rehabilitation treatment. Drive time from each patient's residential address to the closest VA facility where the service was available, measured using geocoded addresses. Binary outcome at the patient level for receipt of osteoporosis screening, spirometry, and cardiac rehabilitation. Multivariable logistic regression models were used to assess associations between drive time and receipt of services. Of 110 780 eligible women analyzed, 36 431 (32.9%) had osteoporosis screening (mean [SD] age, 66.7 [5.4] years; 19 422 [17.5%] Black, 63 403 [57.2%] White). Of 281 130 patients with new COPD diagnosis, 145 249 (51.7%) had spirometry (mean [SD] age, 68.2 [11.5] years; 268 999 [95.7%] men; 37 834 [13.5%] Black, 217 608 [77.4%] White). Of 73 146 patients hospitalized for ischemic heart disease, 11 171 (15.3%) had cardiac rehabilitation (mean [SD] age, 70.0 [10.8] years; 71 217 [97.4%] men; 15 213 [20.8%] Black, 52 144 [71.3%] White). The odds of receiving recommended services declined as drive times increased. Compared with patients with a drive time of 30 minutes or less, patients with a drive time of 61 to 90 minutes had lower odds of receiving osteoporosis screening (adjusted odds ratio [aOR], 0.90; 95% CI, 0.86-0.95) and spirometry (aOR, 0.90; 95% CI, 0.88-0.92) while patients with a drive time of 91 to 120 minutes had lower odds of receiving cardiac rehabilitation (aOR, 0.80; 95% CI, 0.74-0.87). Results were similar in analyses restricted to urban patients or patients whose primary care clinic was in a tertiary care center. In this retrospective cohort study, longer drive time was associated with less frequent receipt of guideline-recommended services across multiple components of care. To improve quality of care and health outcomes, health systems and clinicians should adopt strategies to mitigate travel burden, even for urban patients.

Clinical risk factor status in patients with vertebral fracture but normal bone mineral density

BACKGROUND CONTEXTNormal bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DXA) is present in approximately 10% of older adults with fracture. BMD alone does not evaluate bone quality or clinical risk factors, and therefore, may not adequately capture a patient's fracture risk. Thus, despite a normal DXA-measured BMD, the underlying bone may be abnormal, suggesting that further bone health evaluation, and potentially, pharmacologic treatment may be warranted. PURPOSETo determine the prevalence of normal BMD, clinical fracture risk factors, and quantitative risk of fracture using the Fracture Risk Assessment Tool (FRAX) in vertebral fracture patients with normal BMD enrolled in the Own the Bone registry, thus facilitating identification of those who meet criteria for anti-osteoporosis therapy. STUDY DESIGN/SETTINGRetrospective, national registry-based cohort. PATIENT SAMPLEFrom July 2016 to July 2021, 1,807 patients age ≥50 who sustained a vertebral fracture and had DXA data available from within 2 years prior to enrollment in the American Orthopaedic Association's Own the Bone (AOA OTB) registry were included. OUTCOME MEASURESWorld Health Organization (WHO) DXA T-score based bone classification criteria; FRAX risk scores of major osteoporotic fracture or hip fracture. METHODSDemographic data, prior fracture site, and clinical fracture risk factors were collected. BMD status was classified by the WHO T-score criteria: ≥ -1.0 normal, -1.1 to -2.4 osteopenia, and ≤ -2.5 osteoporosis, with low bone mass including either osteopenia or osteoporosis. In normal BMD patients, FRAX scores were calculated with and without BMD, with the treatment threshold defined as a major osteoporotic fracture risk ≥20% or hip fracture risk ≥3%. RESULTSMean±SD age was 72.0±9.7, 78.1% were female, and 92.4% were Caucasian. Normal BMD was present in 7.9%. Clinical fracture risk factors including alcohol use ≥3 units/day and history of ≥2 falls in the year prior to enrollment were more common in normal BMD (11.2% and 28%, respectively) compared to low bone mass patients (3.4% and 25.2%, respectively). A prior vertebral fracture had occurred in 49.5% with normal BMD compared to 45.8% with low bone mass, while a prior non-major osteoporotic fracture occurred in 28.9% and 29.3% of normal BMD and low bone mass patients, respectively. In normal BMD patients, either a prior fracture or FRAX risk with BMD meeting treatment thresholds was present in 85%. CONCLUSIONSClear indications for receipt of pharmacologic therapy, ie, prior fracture or elevated fracture risk, were present in most patients with vertebral fracture and normal BMD enrolled in the AOA OTB. Prior non-major osteoporotic fractures were common and may be useful indicators of underlying bone disease. Surgeons must recognize that other important risk factors apart from BMD may indicate poor bone health, and thus, help guide further bone health evaluation.

Bridging the Gap: Bone Health Education for Specialists

Our recent scoping review of the perceptions about the importance of treating fractures and osteoporosis among key stakeholders showed the literature on the perceptions of specialist physicians is very limited. Existing literature suggests that recognition of fragility fractures as a sign of underlying bone disease is still low, even among physicians. To increase awareness of osteoporosis as the underlying cause of fragility fracture among specialist physicians who treat patients at high risk of fragility fracture. We have produced a series of educational modules directed at the specialists who would typically treat patients with an increased risk of osteoporosis and fragility fracture due to glucocorticoid use, a plethora of medical conditions or immobility. N/A We are looking to present these materials across the Asia Pacific region in 2022 and beyond. The modules will be available free of charge through the Asia Pacific Fragility Fracture Alliance website ( https://apfracturealliance.org ) and we encourage leaders of all specialties to help raise awareness and increase the rates of osteoporosis identification, diagnosis and management in at-risk populations.

Cardiopulmonary Resuscitation Induced Posterior Rib Fractures in Nontraumatic Pediatric Deaths.

Posterior rib fractures are considered suspicious for nonaccidental injury when observed in infants without significant trauma history or underlying bone disease. The biomechanical mechanism postulated for causing posterior rib fractures is anterior/posterior compression of the chest with posterior levering of the rib head over the transverse process of the vertebra creating a focal area of stress. The recommended "2-thumb" cardiopulmonary resuscitation method involves the administrator placing both thumbs on the sternum of the patient, encircling the chest with the hands, and placing the finger tips lateral to the spine. From this position, the administrator compresses the chest in an anterior/posterior direction by pressing on the sternum. Theoretically, the 2-thumb method should focus all force on the sternum while the back is supported by the fingers limiting posterior levering of the ribs and reducing the risk of posterior rib fractures. However, posterior rib fractures have been found during the autopsy of infants who received 2-thumb cardiopulmonary resuscitation, had no traumatic history, had a nontraumatic cause of death, and had no indication of underlying bone disease. This case study series presents the demographics, birth histories, circumstances surrounding death, and autopsy findings of four such medical examiner cases.

Osteonecrosis of the Jaw and Antiresorptive Agents in Benign and Malignant Diseases: A Critical Review Organized by the ECTS.

ContextAntiresorptive therapy significantly reduces fracture risk in patients with benign bone disease and skeletal-related events (SREs) in patients with bone metastases (BM). Osteonecrosis of the jaw (ONJ) is a rare but severe condition manifested as necrotic bone lesion or lesions of the jaws. ONJ has been linked to the use of potent antiresorptive agents, termed medication-related ONJ (MRONJ).ObjectiveWe aimed to identify the differences various aspects of MRONJ among distinct patient categories and provide recommendations on how to mitigate the risk and optimally manage MRONJ in each of them.MethodsA working group of the European Calcified Tissue Society (ECTS) and 2 experts performed an updated detailed review of existing literature on MRONJ incidence, characteristics, and treatment applied in bone diseases with variable severity of skeletal insult, ranging from osteoporosis to prevention of cancer treatment–induced bone loss and SREs in cancer patients with BM.ResultsThe risk for MRONJ is much higher in patients with advanced malignancies compared to those with benign bone diseases because of the higher doses and more frequent administration of antiresorptive agents in individuals with compromised general health, along with coadministration of other medications that predispose to MRONJ. The overall risk for MRONJ is considerably lower than the benefits in all categories of patients.ConclusionThe risk for MRONJ largely depends on the underlying bone disease and the relevant antiresorptive regimen applied. Physicians and dentists should keep in mind that the benefits of antiresorptive therapy far outweigh the risk for MRONJ development.

Why Mechanism Matters: A Literature Review of Simultaneous Ipsilateral Tibial Tuberosity Avulsion and Patella Fracture With Case Report

Simultaneous ipsilateral tibial tuberosity avulsion and patella fractures are rare in adults. They are often associated with patients who have underlying bone disease and other medical co-morbidities. Here we describe a case where this injury was attributed to direct trauma and demonstrate our department’s management for such an injury. In addition to our case report, we have performed a systematic literature review to identify other cases of the same injury. Only four other cases have been reported. Here we summarise and compare the management and outcome measures reported in each case.All patients are managed differently, yet all authors report satisfactory outcomes. With this being a relatively rare injury, further research is required to establish a gold standard for management of such patients.

Secondary prevention of minor trauma fractures: the effects of a tailored intervention-an observational study.

Minor trauma fractures (MTF) in the elderly are associated with an increase in mortality, morbidity, and the risk of subsequent fractures. Often, these patients who sustain MTF have an underlying bone disease, such as osteopenia or osteoporosis. Osteoporosis is known to be underdiagnosed and undertreated, and adequate treatment is essential to reduce the occurrence of MTFs. At our hospital, this has led to the implementation of Osteofit, a patient-education-based intervention targeted at improving screening and prevention of osteoporosis, with the goal to reduce the rate of subsequent MTF. The aim of this study was to assess the efficacy of Osteofit in improving osteoporosis screening and treatment in patients after an initial MTF episode. The study is a prospective, single-center, cohort study of MTF patients aged 50years or older. A standardized questionnaire and telephone interview were used to collect 1-year follow-up data. The primary outcome was the rate of patients undergoing Dual X-ray Absorptiometry (DXA) scanning. Secondary outcomes were the rate of patients with a diagnosis of osteoporosis or osteopenia, the rate of patients treated with anti-osteoporotic medication, and the rate of patients with a subsequent fracture. DXA scanning rate, the prevalence of a diagnosis (osteoporosis/osteopenia), and data on medical treatment for osteoporosis were compared to the results of a previous study in the same hospital, published in 2004. Between 2012 and 2015, 411 of 823 eligible patients consented to participate and were included in this study. The mean age was 72 ± 9.3years. Sixty-three percent (63.3%, n= 252) of the patients received a DXA scan, compared to 12.6% reported in our previous study. Of all patients who received a DXA scan, 199 (82.9%) were diagnosed with osteoporosis or osteopenia. A total of 95 patients (23.1%) received specific medical treatment for osteoporosis and 59.8% reported the intake of any unspecific medication (vitamin D, calcium, or both). Fifteen patients (3.9%) had a subsequent fracture as a result of a minor trauma fall. The implementation of a MTF secondary prevention program with dedicated health professionals improved the rate of patients who underwent DXA screening by fivefold. Despite this improvement, DXA screening was missed in over a third of patients, with only 23% of eligible patients receiving specific medical treatment for osteoporosis at 1-year follow-up. Consequently, this tailored intervention is a promising first step in improving geriatric fracture care. However, further work to improve the rate of osteoporosis screening and medical treatment initiation for the long-term prevention of subsequent MTF is recommended. We believe osteoporosis screening and adequate osteoporosis medication should be integrated as standard procedure in the aftercare of MTF. II.

A Review and Clinical Perspective of the Impact of Osteoporosis on the Spine.

Introduction:Osteopenia and osteoporosis are common conditions in the United States. The health consequences of low bone density can be dire, from poor surgical outcomes to increased mortality rates following a fracture.Significance:This article highlights the impact low bone density has on spine health in terms of vertebral fragility fractures and its adverse effects on elective spine surgery. It also reviews the clinical importance of bone health assessment and optimization.Results:Vertebral fractures are the most common fragility fractures with significant consequences related to patient morbidity and mortality. Additionally, a vertebral fracture is the best predictor of a subsequent fracture. These fractures constitute sentinel events in osteoporosis that require further evaluation and treatment of the patient’s underlying bone disease. In addition to fractures, osteopenia and osteoporosis have deleterious effects on elective spine surgery from screw pullout to fusion rates. Adequate evaluation and treatment of a patient’s underlying bone disease in these situations have been shown to improve patient outcomes.Conclusion:With an increased understanding of the prevalence of low bone mass and its consequences as well an understanding of how to identify these patients and appropriately intervene, spine surgeons can effectively decrease the rates of adverse health outcomes related to low bone mass.

Association of Bone Mineral Density With Fractures Across the Spectrum of Chronic Kidney Disease: The Regina CKD-MBD Study.

Background:Recent studies have demonstrated that measurement of areal bone mineral density by dual-energy x-ray absorptiometry (DXA) predicts fractures in patients with chronic kidney disease (CKD). However, whether fracture risk prediction through bone mineral density (BMD) is enhanced due to the assessment of biochemical markers of chronic kidney disease and mineral and bone disease (CKD-MBD) or clinical risk factors is not clear. We hypothesized that in a select cohort of patients managed in a CKD clinic, that combining T-Scores with biochemical markers would optimize fracture discrimination than using DXA alone.Objective:To examine the relationships among BMD, biochemical markers of CKD-MBD, and fracture risk across Kidney Disease Improving Global Outcomes (KDIGO) glomerular filtration rate (GFR) categories G3a to G5.Design:Retrospective study.Setting:Patients were recruited from the multidisciplinary CKD clinic, Regina General Hospital, Canada.Patients:A total of 374 patients who received a DXA scan upon initial referral to Regina Multidisciplinary CKD Program from January 31, 2001 to January 31, 2010, were included in this study. The patients were followed for a total of 5 years.Methods:We conducted a retrospective review of 374 consecutive patients who underwent DXA imaging at the point of entry into our multidisciplinary CKD program. Areal BMD, T- and Z-Scores were obtained at the lumbar spine, total hip, mean of left and right femoral neck, and the one-third radius. We collected data on demographic, cross-sectional biochemical markers of mineral metabolism and fractures (identified through self-reported questionnaires, hospital electronic medical records, and physician billing records). We were able to gather data on 8/11 variables of Fracture Risk Assessment (FRAX) tool.Results:In our cohort, 14.3% of GFR categories G3a and G3b, 15.7% of GFR category G4, and 19.7% of GFR category G5 experienced a clinical fracture during the study period. On multivariate analysis, each decline of 1.0 SD in total hip BMD T-Score was associated with a significant increase in the risk of fracture (OR = 1.46, 95% confidence interval [CI], 1.12-1.89). Adding CKD-MBD markers and clinical risk factors did not further contribute to the model. Low BMD was the only independent risk factor for fracture in patients with CKD.Limitations:Self-reporting by patients and administrative records were used to identify fractures. We did not perform spine imaging to ascertain morphometric vertebral fractures. We were unable to gather all 11 variables of FRAX score and information on ethnicity. We were unable to capture site of fracture (hips, spine, etc) from billing records. Albumin excretion rates were not collected at baseline. Treatment of the underlying bone disease with pharmacotherapeutic agents may have attenuated patients’ fracture risk and thus underestimated the association between BMD and future fracture.Conclusions:Our findings confirm that BMD predicts fracture. The addition of cross-sectional CKD-MBD parameters and clinical risk factors to BMD did not add to fracture prediction. Prospective studies should investigate the utility of longitudinal biochemical markers on improving fracture risk assessment.

Update on the Comprehensive Approach to Fragility Fractures.

The prevention and treatment of fragility fractures continuously evolve. Adequate fracture care should involve treating the fracture itself and the underlying bone disease. Although effective treatments of osteoporosis are available, a large proportion of patients with fragility fractures are not prescribed antiosteoporotic medications after their injury. Recent advances in diagnostic tools, medications, and implementation of Fracture Liaison Services allow for more effective and comprehensive treatment or fragility fractures. In the Fracture Liaison Service model, a physician and physician extenders coordinate care. This includes a thorough medical and surgical history, metabolic bone disease laboratory testing, dual-energy x-ray absorptiometry screening, treatment, and long-term follow-up. Treatment options include nonpharmacologic treatment with calcium and vitamin D and antiresorptive and anabolic agents. Antiresorptive agents such as bisphosphonates and denosumab are first-line treatments for osteoporosis and anabolic agents such as teriparatide are effective in reducing bone density loss and have implications in fracture healing. In addition, new anabolic agents including antisclerostin antibodies and parathyroid hormone-related protein show promise as potential treatments to increase bone density.

Patient-Related Factors Associated with Adherence to Recommendations Made by a Fracture Liaison Service: A Mixed-Method Prospective Study.

A Fracture Liaison Service (FLS) has been calculated to be a cost-effective model of care for patients with fragility fracture (FF). Cost-effectiveness can be achieved when adherence to bone health recommendations from FLS staff is high. This prospective study combined participants’ telephone longitudinal survey data (intervention group, n = 354) and interviews with 16 individuals from FLS in three health regions of the province of Quebec (Canada). Participants were recruited between January 2013 and April 2015. Regression models were fit to examine the relationship between participant-related factors and adherence at 12 months to osteoporosis medication, vitamin D supplementation, and participation in physical activity. Participants acknowledging FF as a consequence of osteoporosis were more likely to adhere to medication (odds ratio (OR) 2.5; p = 0.001) and vitamin D supplementation (OR 2.3; p = 0.01). Paradoxically, the same participants were less prone to engage in physical activity (OR 0.5, p = 0.01). Qualitative interviews suggested that feedback from FLS coordinators helped participants understand the underlying cause of their FF. This study highlighted the key roles of FLS staff in helping patients to recognize FF as a sign of underlying bone disease and encouraging adherence to care recommendations.

Using a sequential explanatory mixed method to evaluate the therapeutic window of opportunity for initiating osteoporosis treatment following fragility fractures

A fragility fracture (FF) event identifies patients most likely to benefit from osteoporosis treatment. Nonetheless, most FF patients go untreated. Our objective was to determine how long an incident FF remains a strong incentive to initiate osteoporosis treatment. A total of 1086 men and women over age 50 with a recent FF event were assigned to either standard care (SC), to minimal (MIN), or intensive (INT) interventions targeting patients and their family physician to initiate osteoporosis treatment. Inpatients with FF (mainly hip) evaluated by rheumatologists were also included in a specialized group (SPE; n = 324). At 1year, untreated patients in both the SC and the MIN groups were offered an INT intervention. The cohort was followed through 48months. A qualitative analysis of patient-centered decision-making associated with initiation of treatment was conducted. In MIN and INT groups, osteoporosis treatment was initiated in 41.0 and 54.3% of untreated patients by 12months, respectively, compared to 68.4% in SPE and 18.9% in SC groups; initiation rates drastically dropped thereafter. Over 4863 patient-years of follow-up, the rates of new FF were 3.4 per 100 patient-years, without significant differences between patients with initial major or minor FF, nor between control or intervention groups. Failure by patients and physicians to recognize FF as a sign of underlying bone disease contributed the most to lack of treatment. While incident FFs are an ideal opportunity for starting osteoporosis treatment, 1year later, the therapeutic window of opportunity has already closed.

Altered interaction and distribution of glycosaminoglycans and growth factors in mucopolysaccharidosis type I bone disease

The mucopolysaccharidoses (MPSs) comprise a group of lysosomal storage disorders characterized by deficient degradation and subsequent accumulation of glycosaminoglycans (GAGs). Progressive bone and joint disease are a major cause of morbidity, and current therapeutic strategies have limited effect on these symptoms. By elucidating pathophysiological mechanisms underlying bone disease, new therapeutic targets may be identified. Longitudinal growth is regulated by interaction between GAGs and growth factors. Because GAGs accumulate in the MPSs, we hypothesized that altered interaction between growth factors and GAGs contribute to the pathogenesis of MPS bone disease. In this study, binding between GAGs from MPS I chondrocytes and fibroblast growth factor 2 (FGF2) was not significantly different from binding of FGF2 to GAGs from control chondrocytes. FGF2 signaling, however, was increased in MPS I chondrocytes after incubation with FGF2, as compared to control chondrocytes. Using bone cultures, we demonstrated decreased growth of WT mouse bones after incubation with FGF2, but no effect on MPS I bone growth. However, MPS I bones showed decreased growth in the presence of GAGs from MPS I chondrocytes. Finally, we demonstrate altered GAG distribution in MPS I chondrocytes, and altered GAG, FGF2 and Indian hedgehog distribution in growth plates from MPS I mice. In summary, our results suggest that altered interaction and distribution of growth factors and accumulated GAGs may contribute to the pathogenesis of MPS bone disease. In the future, targeting growth factor regulation or the interaction between in growth factors and GAGs might be a promising therapeutic strategy for MPS bone disease.

Pathological and metabolic bone diseases: Clinical importance for fracture treatment

Pathological and metabolic bone diseases are common and relevant occurrences in orthopedics and trauma surgery; however, fractures are often treated as being the illness itself and not seen as the symptom of an underlying bone disease. This is why further diagnostics and systemic treatment options are often insufficiently considered in the routine treatment of fractures. This review focuses on osteoporosis, osteopetrosis, hypophosphatasia and Paget's disease of bone.In patients with osteoporotic vertebral or proximal femur fractures, pharmaceutical treatment to prevent subsequent fractures is an integral part of fracture therapy together with surgical treatment. Osteopetrosis is caused by compromised osteoclastic bone resorption; therefore, even in the face of an elevated bone mass, vitamin D3 supplementation is crucial to avoid clinically relevant hypocalcemia. Unspecific symptoms of the musculoskeletal system, especially together with stress fractures, are typically found in patients suffering from hypophosphatasia. In these patients measurement of alkaline phosphatase shows reduced enzyme activity. Elevated levels of alkaline phosphatase are found in Paget's disease of bone where bisphosphonates are still the treatment of choice.

Fifty shades of gray: Bone disease in renal transplantation

Kidney transplantation is the renal replacement therapy of choice for patients with end stage renal disease. Advances in technology, surgical techniques and pharmacotherapy have improved renal allograft survival. Increasingly, we are seeing long term side effects related to renal transplantation, bone disease being a major one amongst them. Renal transplant patients have a higher risk of fragility fractures even when compared to those who remain on dialysis. This is likely to be related to pre-existing underlying bone disease and the emergence of new metabolic bone problems post-transplant. Conditions such as persistent hyperparathyroidism and the use of certain immunosuppressive agents have a deleterious effect on the post renal transplant bone. Remarkable advances in the field of metabolic bone research have been made in the last decade and newer imaging techniques, biomarkers and therapeutic options are now available for osteoporosis in the general population. Interest is being focused on attempting to extrapolate these new discoveries to the management of bone disease post renal transplant. This review will briefly describe the metabolic bone changes that occur after transplantation and will provide an update on the currently available investigative options and therapeutic strategies for the management of post renal transplant bone disease.

Animal model for medication-related osteonecrosis of the jaw with precedent metabolic bone disease

Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis.Ninty-six rats were randomly divided into ovariectomy (Ov) group (n=48) and sham-operated group (n=48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n=36 each) and control group (n=12 each) and injected with zoledronic acid and normal saline, respectively, once a week. After additional 6weeks, surgical intervention was performed, and the injections were continued for 8 more weeks. The animals were then sacrificed for further macroscopic, histological, histomorphometric, radiological, and bone biomarker investigations.As histologically determined, the Ov group (77.8%) showed higher ONJ prevalence compared to the sham group (47.2%; P<0.05). Micro-structural and histomorphometric assessments revealed that rats with ONJ (ONJ group) presented with deteriorated bone architectures with higher necrotic bone fraction and lower number of osteoclasts (P<0.05). Compared to the sham-operated ONJ group, the Ov ONJ group showed significantly lower values of Tb.N, Tb.Sp, Conn.D, N.Oc/T.Ar, and TRACP 5b and CTX/TRACP (P<0.05).The ovariectomized rat model in this study successfully mimicked human ONJ lesions with an underlying bone disease and showed different bone characteristics than that of the previous ONJ model. Based on the differences, further researches for investigating pathophysiology of ONJ, including various pharmacological responses for deteriorated bone environment, are required.

Bone health in prostate cancer patients: A survivorship issue requiring intervention.

247 Background: In general, men are not routinely screened for bone health. Prostate cancer patients are at an increased risk because of treatment with androgen deprivation therapy (ADT). Unlike other patients diagnosed with a malignancy, they may survive a long time. Some risk factors include inadequate calcium, vitamin D deficiency, tobacco use and alcohol abuse. We implemented a pre-ADT program to mitigate the effects of ADT on bone health. This study evaluates the pre-existing risk factors and bone health by baseline DEXA scans pre-ADT initiation. Methods: We completed a chart review of 182 veterans referred to Radiation Oncology for curative treatment of prostate cancer from 2009 to 2013. Of those, 160 patients underwent baseline DEXA scans. Clinical variables analyzed were demographics, tobacco and alcohol use, vitamin D levels, incidence of AODM (adult onset diabetes mellitus), and calcium or vitamin D intervention. Descriptive statistics and bivariate analysis including Chi Square tests and odds ratios were carried out. Results: The mean age of the study participants was 66.6 years (range 47-82.8 years). Baseline DEXA scans were abnormal in 63% of patients, showing osteoporosis and/or osteopenia. Vitamin D levels were abnormal in 61% of patients- 26% of whom had normal DEXA scans. Twenty percent had a history of alcohol abuse, and 56% used tobacco; 33% had AODM. Smokers with an abnormal Vitamin D level were at increased risk of bone disease as compared to non smokers (OR 3.23, 95% CI 1.35-7.69 p&lt;0.01). Variables significantly impacting bone health were age (OR 1.087, p=0.012, 95% CI 1.018-1.161) and Tobacco use (OR 0.424, p=0.045, 95% CI 0.183-0.980). Almost 90% of the patients in this study had intermediate risk prostate cancer with an expected cancer specific survival of 85 to 90% at 5 to 10 years. Conclusions: Pre-ADT screening confirms the risk of underlying bone disease in this veteran population with an expectation of long term survival. Guidelines for treatment and prevention of bone disease should be implemented in all patients over age of 50. Particular attention should be paid to patients who underwent ADT. This can affect the quality of life in this group of cancer survivors.

Bone health in prostate patients: An opportunity for screening and intervention.

9623 Background: Despite known risk factors, men are not routinely screened for bone health. Men with prostate cancer are at an increased risk of bone disease because of treatment with androgen deprivation therapy (ADT). Risk factors include family history, calcium and vitamin D deficiency, certain medications, being thin or small-boned, tobacco use, alcohol abuse. and lack of physical activity. We started a screening and management program to mitigate the effects of ADT on bone health in veterans beginning treatment for prostate cancer. This study evaluates the pre-existing risk factors in pts who had baseline dexa scans before ADT. Methods: We completed a retrospective chart review of 182 veterans diagnosed with prostate cancer and referred to Radiation Oncology for radical treatment from 2009 to 2013. This reports on the 160 pts who had baseline dexa scans. Clinical variables analyzed were demographics, tobacco and alcohol use, vitamin D levels, incidence of AODM (adult onset diabetes mellitus), and calcium or vitamin D use. Descriptive statistics as well as bivariate analysis including Chi Square tests and odds ratios were calculated. Results: The mean age of the study participants was 66.6 yrs (47-82.8 yrs); 52% were African American, 45% White, 3% Hispanic. Baseline dexa scans were abnormal in 63% of pts, showing osteoporosis and /or osteopenia. Vitamin D levels were abnormal in 61%. Abnormal vitamin D levels were found in 26% of pts with normal DEXA scans. Almost 99% pts received calcium and Vitamin D supplements. Twenty percent had a history of alcohol abuse, 56% used tobacco, and 33% had AODM. Ethnicity may be a factor ( p<0.05) but the sample sizes per group were not equivalent. Smokers with an abnormal Vitamin D level were at increased risk of bone disease as comparedto non smokers (p<0.01) . Conclusions: Pre-ADT screening confirms the risk of underlying bone disease in this previously unscreened veteran population. Guidelines for treatment and prevention of bone disease should be implemented in all patients over age of 50. An opportunity exists to identify and treat men at risk when seen for prostate cancer treatment whether they receive ADT or not.