Outcomes following hip fracture surgery in adults with schizophrenia in Ontario, Canada: A 10-year population-based retrospective cohort study.

OBJECTIVE: To understand immediate and long-term outcomes following hip fracture surgery in adults with schizophrenia. METHODS: Retrospective population-based cohort study leveraging health administrative databases from Ontario, Canada. Individuals aged 40-105 years with hip fracture surgery between April 1, 2009 and March 31, 2019 were included. Schizophrenia was ascertained using a validated algorithm. Outcomes were: 30-day mortality; 30-day readmission; 1-year survival; and subsequent hip fracture within 2 years. Analyses incorporated Generalized Estimating Equation models, Kaplan-Meier curves, and Fine-Gray competing risk models. RESULTS: In this cohort study of 98,126 surgically managed hip fracture patients, the median [IQR] age was 83[75-89] years, 69.2% were women, and 3700(3.8%) had schizophrenia. In Fine-Gray models, schizophrenia was associated with subsequent hip fracture (sdRH, 1.29; 95% CI, 1.09-1.53), with male patients with schizophrenia sustaining a refracture 50 days earlier. In age- and sex-adjusted GEE models, schizophrenia was associated with 30-day mortality (OR, 1.31; 95% CI, 1.12-1.54) and readmissions (OR, 1.40; 95% CI, 1.25-1.56). Kaplan-Meier survival curves suggested that patients with schizophrenia were less likely to be alive at 1-year. CONCLUSIONS: Study highlights the susceptibility of hip fracture patients with schizophrenia to worse outcomes, including refracture, with implications for understanding modifiable processes of care to optimize their recovery.

Association of Different Prescribing Patterns for Oral Corticosteroids With Fracture Preventive Care Among Older Adults in the UK and Ontario.

Importance: Identifying and mitigating modifiable gaps in fracture preventive care for people with relapsing-remitting conditions such as eczema, asthma, and chronic obstructive pulmonary disease who are prescribed high cumulative oral corticosteroid doses may decrease fracture-associated morbidity and mortality. Objective: To estimate the association between different oral corticosteroid prescribing patterns and appropriate fracture preventive care, including treatment with fracture preventive care medications, among older adults with high cumulative oral corticosteroid exposure. Design, Setting, and Participants: This cohort study included 65 195 participants with UK electronic medical record data from the Clinical Practice Research Datalink (January 2, 1998, to January 31, 2020) and 28 674 participants with Ontario, Canada, health administrative data from ICES (April 1, 2002, to September 30, 2020). Participants were adults 66 years or older with eczema, asthma, or chronic obstructive pulmonary disease receiving prescriptions for oral corticosteroids with cumulative prednisolone equivalent doses of 450 mg or higher within 6 months. Data were analyzed October 22, 2020, to September 6, 2022. Exposures: Participants with prescriptions crossing the 450-mg cumulative oral corticosteroid threshold in less than 90 days were classified as having high-intensity prescriptions, and participants crossing the threshold in 90 days or more as having low-intensity prescriptions. Multiple alternative exposure definitions were used in sensitivity analyses. Main Outcomes and Measures: The primary outcome was prescribed fracture preventive care. A secondary outcome was major osteoporotic fracture. Individuals were followed up from the date they crossed the cumulative oral corticosteroid threshold until their outcome or the end of follow-up (up to 1 year after index date). Rates were calculated for fracture preventive care and fractures, and hazard ratios (HRs) were estimated from Cox proportional hazards regression models comparing high- vs low-intensity oral corticosteroid prescriptions. Results: In both the UK cohort of 65 195 participants (mean [IQR] age, 75 [71-81] years; 32 981 [50.6%] male) and the Ontario cohort of 28 674 participants (mean [IQR] age, 73 [69-79] years; 17 071 [59.5%] male), individuals with high-intensity oral corticosteroid prescriptions had substantially higher rates of fracture preventive care than individuals with low-intensity prescriptions (UK: 134 vs 57 per 1000 person-years; crude HR, 2.34; 95% CI, 2.19-2.51, and Ontario: 73 vs 48 per 1000 person-years; crude HR, 1.49; 95% CI, 1.29-1.72). People with high- and low-intensity oral corticosteroid prescriptions had similar rates of major osteoporotic fractures (UK: crude rates, 14 vs 13 per 1000 person-years; crude HR, 1.07; 95% CI, 0.98-1.15 and Ontario: crude rates, 20 vs 23 per 1000 person-years; crude HR, 0.87; 95% CI, 0.79-0.96). Results from sensitivity analyses suggested that reaching a high cumulative oral corticosteroid dose within a shorter time, with fewer prescriptions, or with fewer or shorter gaps between prescriptions, increased fracture preventive care prescribing. Conclusions: The results of this cohort study suggest that older adults prescribed high cumulative oral corticosteroids across multiple prescriptions, or with many or long gaps between prescriptions, may be missing opportunities for fracture preventive care.

Ankle flexor torque, size and density are differential determinants of distal tibia trabecular plate-rod morphometry and bone strength: The Ankle Quality Study.

HYPOTHESIS: Greater peak torque and higher myotendinous density at the ankle are associated with a more plate-like architecture at the distal tibia. METHODS: In this cross-sectional study, women and men ≥ 50 years old with no metal implants, reconstructive surgery, muscular dystrophies, or tendinopathies in any leg were recruited by convenience. Isometric ankle dorsi-plantar flexion and inversion-eversion peak torques were measured using dynamometry. HR-pQCT distal tibia scans were completed. Both assessments were completed on the same day on the non-dominant leg. Integral and trabecular vBMD were derived from standard analyses, failure load (FL) was obtained from finite element analysis, plate-specific parameters were computed from individual trabecula segmentation (ITS) analysis, myotendinous density (MyD) and volume fraction (MyV/TV) were computed from soft tissue analysis. pQCT scans of the 66 % mid-leg were performed (500 µm at 15 mm/s) to obtain muscle density (MD) and muscle cross-sectional area (MCSA). STATISTICAL ANALYSIS: General linear models estimated how ankle muscle group torque and muscle size and density differentially related, both separately and together, to whole-bone properties (integral vBMD, FL) and trabecular morphometry (ITS plate parameters). Models were adjusted for age, sex, BMI, use of glucocorticoids, current osteoarthritis, and participation in moderate to vigorous recreational or sport activities. RESULTS: Among 105 participants (77 % female, mean age: 63 (10) years, BMI: 25.8 (5.4) kg/m2, 25 % with OA, 17 % fracture history, 42 % falls history), all torque measures, particularly ankle dorsiflexion and eversion, were correlates of plate-plate/rod junction density and failure load. However, muscle size and density measures were further associated with vBMD. The effect of greater ankle flexor-extensor torque on more connected bone was stronger when MyD was higher (interaction p < 0.001). CONCLUSION: Strength of muscles around the ankle are correlates of plate-like trabeculae at the distal tibia, while leaner muscle and myotendinous tissues facilitates better quality bone for stronger ankle muscle torque.

Variation in bone mineral density and fractures over 20 years among Canadians: a comparison of the Canadian Multicenter Osteoporosis Study and the Canadian Longitudinal Study on Aging.

International variations in osteoporosis and fracture rates have been reported, with temporal trends differing between populations. We observed higher BMD and lower fracture prevalence in a recently recruited cohort compared to that of a cohort recruited 20 years ago, even after adjusting for multiple covariates. PURPOSE: We explored sex-specific differences in femoral neck bone mineral density (FN-BMD) and in prevalent major osteoporotic fractures (MOF) using two Canadian cohorts recruited 20 years apart. METHODS: We included men and women aged 50-85 years from the Canadian Multicentre Osteoporosis Study (CaMos, N = 6,479; 1995-1997) and the Canadian Longitudinal Study on Aging (CLSA, N = 19,534; 2012-2015). We created regression models to compare FN-BMD and fracture risk between cohorts, adjusting for important covariates. Among participants with prevalent MOF, we compared anti-osteoporosis medication use. RESULTS: Mean (SD) age in CaMos (65.4 years [8.6]) was higher than in CLSA (63.8 years [9.1]). CaMos participants had lower mean body mass index and higher prevalence of smoking (p < 0.001). Adjusted linear regression models (estimates [95%CI]) demonstrated lower FN-BMD in CaMos women (- 0.017 g/cm2 [- 0.021; - 0.014]) and men (- 0.006 g/cm2 [- 0.011; 0.000]), while adjusted odds ratios (95%CI) for prevalent MOF were higher in CaMos women (1.99 [1.71; 2.30]) and men (2.33 [1.82; 3.00]) compared to CLSA. In women with prevalent MOF, menopausal hormone therapy use was similar in both cohorts (43.3% vs 37.9%, p = 0.076), but supplements (32.0% vs 48.3%, p < 0.001) and bisphosphonate use (5.8% vs 17.3%, p < 0.001) were lower in CaMos. The proportion of men with MOF who received bisphosphonates was below 10% in both cohorts. CONCLUSION: Higher BMD and lower fracture prevalence were noted in the more recently recruited CLSA cohort compared to CaMos, even after adjusting for multiple covariates. We noted an increase in bisphosphonate use in the recent cohort, but it remained very low in men.

MoveStrong at home: a feasibility study of a model for remote delivery of functional strength and balance training combined with nutrition education for older pre-frail and frail adults.

Exercise and nutrition interventions are often recommended for frailty; however, effective strategies are required for real-world implementation. Our primary aim was to assess the feasibility and acceptability of telephone and virtual delivery of MoveStrong, an 8-week exercise and nutrition program with a 4-week follow-up for older pre-frail and frail adults. A priori criteria for success included: recruitment (≥25/12 weeks), retention at follow-up (≥80%), and adherence to exercise and nutrition sessions (≥70%). We recruited community-dwelling Ontario residents; ≥60 years, ≥1 chronic condition, ≥1 FRAIL scale score. Participants received mailed materials, a personalized exercise program, 11 remote one-on-one training sessions with an exercise physiologist and 3 online dietitian-led nutrition education sessions. We completed exploratory analyses of secondary outcomes including physical function and dietary protein intake. Semi-structured interviews supported program evaluation. In total, 30 participants were enrolled. 28 (93%) participants completed program and follow-up assessments. Adherence to exercise and nutrition sessions (CI) was 84% (77%-91%) and 82% (70%-93%) respectively. At program end and follow-up [mean change (CI)], significant improvements were measured in 30-second chair stand test [3.50 (1.12-5.86), 4.54 (1.94-7.13) chair stands] and dietary protein intake [12.9 (5.7-20.0), 9.2 (0.4-18.1) g]. Overall, participants were satisfied with program delivery. Trial registration number: NCT04663685.

Implementing and Evaluating the Impact of BoneRx: A Healthy Bone Prescription for Men with Prostate Cancer Initiating Androgen Deprivation Therapy.

Background: The initiation of Androgen Deprivation Therapy (ADT) results in rapid and profound hypogonadism, resulting in significant bone and muscle loss, increasing the risk for osteoporosis (OP), falls, and fractures. Despite this, there exist very low rates of guideline adherent care regarding bone health in this population. We developed and implemented a healthy bone prescription tool entitled BoneRx to facilitate the uptake of guideline-concordant bone health care into practice and increase patient awareness and promote the uptake of health bone behaviours (HBBs). Methods: We conducted a cross-sectional pre-BoneRx implementation (n = 143) vs. post-implementation (n = 149) cohort study to evaluate the impact on (i) bone health care, patient engagement in HBB, and patient knowledge and health beliefs regarding OP. Results: There was a significant difference pre- vs. post BoneRx implementation on receipt of baseline BMD (34.7% vs. 59.5%, p < 0.0001) and bone health counselling (32.4% vs. 59.9%, p < 0.0001). More participants in the post-BoneRx implementation cohort reported taking vitamin D supplements 57% vs. 81% (p < 0.001) and calcium supplements 39% vs. 61% (p < 0.001). Physical activity levels also significantly increased (p = 0.021). No differences were detected in OP knowledge or feelings of OP susceptibility, seriousness, or health motivation. Conclusion: BoneRx is a simple, cost-effective, and acceptable strategy that could improve the care of PCa survivors receiving ADT.

Vitamin K and Kidney Transplantation.

The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches.

Changes in Bone Mineral Density After Prophylactic Bilateral Salpingo-Oophorectomy in Carriers of a BRCA Mutation.

Importance: Preventive surgery is strongly recommended for individuals with a BRCA mutation at a young age to prevent ovarian cancer and improve overall survival. The overall effect of early surgical menopause on various health outcomes, including bone health, has not been clearly elucidated. Objective: To evaluate the association of prophylactic bilateral salpingo-oophorectomy with bone mineral density (BMD) loss among individuals with a BRCA mutation. Design, Setting, and Participants: This retrospective cohort study of participants with a BRCA mutation who underwent oophorectomy through the University Health Network, Toronto, Ontario, Canada, recruited participants from January 2000 to May 2013. Eligibility criteria included having a BRCA mutation, at least 1 ovary intact prior to surgery, and no history of any cancer other than breast cancer. Bone mineral density was measured using dual-energy x-ray absorptiometry before and after surgery. Data analysis began in December 2018 and finished in January 2019. Main Outcomes and Measures: The annual change in BMD from baseline to follow-up was calculated for the following 3 anatomical locations: (1) lumbar spine, (2) femoral neck, and (3) total hip. Results: A total of 95 women had both a baseline and postsurgery BMD measurement with a mean (SD) follow-up period of 22.0 (12.7) months. The mean (SD) age at oophorectomy was 48.0 (7.4) years. Among women who were premenopausal at time of surgery (50 [53%]), there was a decrease in BMD from baseline to follow-up across the lumbar spine (annual change, -3.45%; 95% CI, -4.61% to -2.29%), femoral neck (annual change, -2.85%; 95% CI, -3.79% to -1.91%), and total hip (annual change, -2.24%; 95% CI, -3.11% to -1.38%). Self-reported hormone therapy use was associated with significantly less bone loss at the lumbar spine (-2.00% vs -4.69%; P = .02) and total hip (-1.38% vs -3.21; P = .04) compared with no hormone therapy use. Among postmenopausal women at time of surgery (45 [47%]), there was also a significant decrease in BMD across the lumbar spine (annual change, -0.82%; 95% CI, -1.42% to -0.23%) and femoral neck (annual change, -0.68%; 95% CI, -1.33% to -0.04%) but not total hip (annual change, -0.18%; 95% CI, -0.82% to 0.46%). Conclusions and Relevance: This study found that oophorectomy was associated with postoperative bone loss, especially among women who were premenopausal at the time of surgery. Targeted management strategies should include routine BMD assessment and hormone therapy use to improve management of bone health in this population.

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline.

OBJECTIVE: The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women. CONCLUSIONS: Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in writing committee deliberations. A consensus by the Writing Committee members was achieved for four management principles: (i) The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making. (ii) Patient preferences should be incorporated into treatment planning. (iii) Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk. (iv) Multiple pharmacologic therapies are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles.

Women's Mid-Life Night Sweats and 2-Year Bone Mineral Density Changes: A Prospective, Observational Population-Based Investigation from the Canadian Multicentre Osteoporosis Study (CaMos).

Women's hot flushes and night sweats, collectively called vasomotor symptoms (VMS), are maximal (79%) in late perimenopause. The evidence describing whether VMS are associated with loss of areal bone mineral density (BMD) is mixed. We examined baseline and 2-year data for 1570 randomly selected women aged 43⁻63 in the Canadian Multicentre Osteoporosis Study (CaMos), a prospective Canada-wide study; we used linear regression to assess the relationship of night sweats (VMSn) with BMD and its changes. Clinically important VMSn occurred for 12.2%. Women with VMSn were slightly younger (54.5 vs. 55.3 years, p = 0.02) and less likely to use sex steroid therapies (39.8% vs. 51.4%, p < 0.05). BMD at the lumbar spine (L1-4), femoral neck (FN) and total hip (TH) were similar between those with/without VMSn. In adjusted models, we did not find a significant association between VMSn and 2-year change in L1-4, FN and TH BMD. Age, reproductive status, weight, sex steroid therapy and smoking status were associated with 2-year change in BMD. Incident fractures over 2 years also did not differ by VMSn. Our analyses were restricted to VMSn and may not truly capture the relationship between VMS and BMD. Additional research involving VMS, bone loss and fracture incidence is needed.

Assessment of the effect of strontium, lead, and aluminum in bone on dual-energy x-ray absorptiometry and quantitative ultrasound measurements: A phantom study.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard technique to measure areal bone mineral density (aBMD) for the diagnosis of osteoporosis. Because DXA relies on the attenuation of photon to estimate aBMD, deposition of bone-seeking metallic elements such as strontium, lead, and aluminum that differ in atomic numbers from calcium can cause inaccurate estimation of aBMD. Quantitative ultrasound (QUS) is another technique available to assess bone health by measuring broadband ultrasound attenuation (BUA), speed of sound (SOS), and an empirically derived quantity called stiffness index (SI). Because the acoustic properties are not prone to significant change due to changes in microscopic atomic composition of bone, it is hypothesized that QUS is unaffected by the presence of bone-seeking elements in the bone. The objective of this study was to investigate the effect of strontium, lead, and aluminum on DXA-derived aBMD and QUS parameters using bone-mimicking phantoms compatible with both techniques. METHODS: Bone-mimicking phantoms were produced by homogeneously mixing finely powdered hydroxyapatite compounds that contain varying concentrations of strontium, lead, or aluminum with porcine gelatin solution. Seven strontium-substituted phantoms were produced with varying molar ratio of Sr/(Sr + Ca) ranging from 0% to 2%. Four lead-doped phantoms and four aluminum-doped phantoms were constructed with the respective analyte concentrations ranging from 50 to 200 ppm. An additional 0 ppm phantom was produced to be used as a baseline for the lead and aluminum phantom measurements. All phantoms had uniform volumetric bone mineral density (vBMD) of 200 mg/cm3 , and were assessed using a Hologic Horizon® DXA device and a Hologic Sahara® QUS device. Furthermore, theoretical aBMD bias for mol/mol% substitution of calcium with the three bone-seeking elements was calculated. RESULTS: Strong positive linear relationship was found between aBMD measured by DXA and strontium concentration (P < 0.001, r = 0.995). From the measurement of lead and aluminum phantoms using DXA, no statistically significant relationship was observed between aBMD and the analyte concentrations. For the QUS system, with an exception of BUA and lead concentration that exhibited statistically significant relationship (P < 0.038, r = 0.899), no statistically significant change was observed in all QUS parameters with respect to the clinically relevant concentration of all three elements. The calculated theoretical aBMD bias induced by 1 mol/mol% substitution of calcium with strontium, lead, and aluminum were 10.8%, 4.6%, and -0.7%, respectively. CONCLUSION: aBMD measured by DXA was prone to overestimation in the presence of strontium, but acoustic parameters measured by QUS are independent of strontium concentration. The deviation in aBMD induced by the clinically relevant concentrations of lead and aluminum under 200 ppm could not be detected using the Hologic Horizon® DXA device. Furthermore, the SI measured by the QUS system was not affected by lead or aluminum concentrations used in this study.

Improving bone health in men with prostate cancer receiving androgen deprivation therapy: Results of a randomized phase 2 trial.

BACKGROUND: Strategies to improve bone health care in men receiving androgen deprivation therapy (ADT) are not consistently implemented. The authors conducted a phase 2 randomized controlled trial of 2 education-based models-of-care interventions to determine their feasibility and ability to improve bone health care. METHODS: A single-center parallel-group randomized controlled trial of men with prostate cancer who were receiving ADT was performed. Participants were randomized 1:1:1 to 1) a patient bone health pamphlet and brief recommendations for their family physician (BHP+FP); 2) a BHP and support from a bone health care coordinator (BHP+BHCC); or 3) usual care. The primary efficacy outcome was receipt of a bone mineral density (BMD) test within 6 months. Secondary efficacy outcomes included guideline-appropriate calcium and vitamin D use and bisphosphonate prescriptions for men at high fracture risk. Feasibility endpoints included recruitment, retention, satisfaction, contamination, and outcome capture. The main analysis used logistic regression with a 1-sided P of .10. The trial is registered at ClinicalTrials.gov (identifier NCT02043236). RESULTS: A total of 119 men were recruited. The BHP+BHCC strategy was associated with a greater percentage of men undergoing a BMD test compared with the usual-care group (78% vs 36%; P<.001). BMD ordering also was found to be increased with the BHP+FP strategy (58% vs 36%; P = .047). Both strategies were associated with higher percentages of patients using calcium and vitamin D, but only the BHP+FP arm was statistically significant (P = .039). No men were detected to be at high fracture risk. All but one feasibility endpoint was met. CONCLUSIONS: Educational strategies to improve bone health care appear feasible and are associated with improved BMD ordering in men receiving ADT. Cancer 2018;124:1132-40. © 2017 American Cancer Society.

Drug-Related Adverse Events of Osteoporosis Therapy.

Postmenopausal osteoporosis is associated with microarchitectural deterioration and increased risk of fracture. Osteoporosis therapy effectively reduces the risk of vertebral, nonvertebral, and hip fracture and has been associated with increased survival. Currently approved treatments for osteoporosis include bisphosphonates, denosumab, selective estrogen receptor modulators, and teriparatide. This article reviews the adverse events of therapy associated with these medical interventions. Hormone replacement therapy is not included, because it is no longer indicated for the treatment of osteoporosis in all countries. Calcitonin and strontium ranelate are also not included, because their indication for osteoporosis has recently been limited or withdrawn.

Novel imaging modalities for the comparison of bone microarchitecture among HIV+ patients with and without fractures: a pilot study.

BACKGROUND: HIV-infected adults have increased fracture risk. OBJECTIVES: To generate pilot data comparing bone density, structure, and strength between HIV-infected adults with and without a prior fracture. METHODS: Adults with and without a prior fracture after their HIV diagnosis were matched 1:1 based on age, sex, race, and smoking history. Participants underwent dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), hip structural analyses (HSA), vertebral fracture assessment (VFA), high-resolution peripheral quantitative tomography (HR-pQCT) and measurement of bone turnover markers. Results were compared between cases and controls, with differences expressed as percentages of control group values. RESULTS: 23 pairs were included. On DXA, cases had lower areal bone mineral density (aBMD) at the total hip (median difference in T-score -0.25, p = 0.04), but not the lumbar spine (median difference in T-score 0.10, p = 0.68). Cases had greater abnormalities in HSA and most HR-pQCT and HSA measures, by up to 15%. VFA revealed two subclinical fractures among cases but none among controls. TBS, CTX, and P1NP levels were similar between groups, with differences of 1.9% (p = 0.90), 9.7% (p = 0.55), and 10.0% (p = 0.24), respectively. For each parameter, we report the median and interquartile range for the absolute and relative difference between cases and controls, the correlation between cases and controls, and our recruitment rates, to inform the design of future studies. CONCLUSIONS: These pilot data suggest potential differences in bone structure, estimated bone strength, and asymptomatic vertebral fractures among HIV-infected adults with and without fracture, warranting further study as markers of fracture risk in HIV.

Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ.

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.

Prevalence and risk factors of low bone mineral density in psoriatic arthritis: A systematic review.

OBJECTIVE: Prevalence and impact of low bone mineral density (BMD) in psoriatic arthritis (PsA) is not well understood. We aimed to synthesize current evidence regarding the prevalence, impact, and risk factors for low BMD and fractures in PsA. METHODS: A systematic literature search limited to human studies was conducted without language restriction. Data on BMD, prevalence of osteoporosis, osteopenia and fractures, risk factors, morbidity, and mortality due to low BMD in PsA patients were collected. RESULT: A total of 21 studies (16 case-control, 4 cross-sectional, and 1 prospective cohort) were reviewed after screening 639 titles and abstracts. In all, 17 studies compared PsA patients with one or more control group (four normal controls, five psoriasis, and eight other rheumatic diseases with or without healthy controls). The number of PsA patients in the studies ranged from 8 to 2212 with a mean (standard deviation) age of 35 (10) to 63.4 (6.2), and mean PsA duration of 2.25-13.65 years. Reported prevalence of osteoporosis varied from 1.4% to 68.8%. Low BMD was identified as a significant problem in 13 of the 21 studies. Age, female sex, postmenopausal status, PsA duration, presence of erosions, and cumulative steroid dose were associated with lower BMD. Fractures (12-40%) were associated with postmenopausal status and axial disease. No studies reported on hospitalization and mortality due to low BMD. CONCLUSION: This systematic review synthesizes current evidence on BMD and its impact in PsA. High likelihood of bias and inconsistent results suggest a need for well-designed longitudinal studies on bone health in PsA.

Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis.

BACKGROUND: Adults who require long-term anticoagulation with low-molecular-weight heparin (LMWH) such as cancer patients or the elderly may be at increased risk of fractures. OBJECTIVE: To determine the effects of LMWH therapy of at least 3 months' duration on fractures and bone mineral density (BMD) in non-pregnant adult populations. METHODS: We systematically reviewed electronic databases (e.g., MEDLINE, EMBASE), conferences and bibliographies until June 2015 and included comparative studies in non-pregnant adult populations that examined the effects of LMWH (≥3 months) on fractures and BMD. We synthesized evidence qualitatively and used random-effects meta-analysis to quantify the effect of LMWH on fractures. RESULTS: Sixteen articles reporting 14 studies were included: 10 clinical trials (n = 4865 participants) and four observational cohort studies (3 prospective, n = 221; 1 retrospective, n = 30). BMD and fractures were secondary outcomes in the majority of trials, while they were primary outcomes in the majority of observational studies. In participants with venous thromboembolism and underlying cardiovascular disease or cancer (5 RCTs, n = 2280), LMWH for 3-6 months did not increase the relative risk of all fractures at 6-12 months compared to unfractionated heparin, oral vitamin K antagonists or placebo [pooled risk ratio (RR) = 0.58, 95 % CI: 0.23-1.43; I(2) = 12.5 %]. No statistically significant increase in the risk of fractures at 6-12 months was found for cancer patients (RR = 1.08, 95 % CI: 0.31-3.75; I(2) = 4.4 %). Based on the data from two prospective cohort studies (n = 166), LMWH for 3-24 months decreased mean BMD by 2.8-4.8 % (depending on the BMD site) compared to mean BMD decreases of 1.2-2.5 % with oral vitamin K antagonists. CONCLUSIONS: LMWH for 3-6 months may not increase the risk of fractures, but longer exposure for up to 24 months may adversely affect BMD. Clinicians should consider monitoring BMD in adults on long-term LMWH who are at increased risk of bone loss or fracture.

Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus.

This work provides a systematic review of the literature from January 2003 to April 2014 pertaining to the incidence, pathophysiology, diagnosis, and treatment of osteonecrosis of the jaw (ONJ), and offers recommendations for its management based on multidisciplinary international consensus. ONJ is associated with oncology-dose parenteral antiresorptive therapy of bisphosphonates (BP) and denosumab (Dmab). The incidence of ONJ is greatest in the oncology patient population (1% to 15%), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of ONJ is estimated at 0.001% to 0.01%, marginally higher than the incidence in the general population (<0.001%). New insights into the pathophysiology of ONJ include antiresorptive effects of BPs and Dmab, effects of BPs on gamma delta T-cells and on monocyte and macrophage function, as well as the role of local bacterial infection, inflammation, and necrosis. Advances in imaging include the use of cone beam computerized tomography assessing cortical and cancellous architecture with lower radiation exposure, magnetic resonance imaging, bone scanning, and positron emission tomography, although plain films often suffice. Other risk factors for ONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures, as well as other drugs, including antiangiogenic agents. Prevention strategies for ONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of ONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of ONJ is based on the stage of the disease, size of the lesions, and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Localized surgical debridement is indicated in advanced nonresponsive disease and has been successful. Early data have suggested enhanced osseous wound healing with teriparatide in those without contraindications for its use. Experimental therapy includes bone marrow stem cell intralesional transplantation, low-level laser therapy, local platelet-derived growth factor application, hyperbaric oxygen, and tissue grafting.