The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients.

Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. METHODS: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), ß-C-terminal telopeptide of type I collagen (ß-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. RESULTS: The area under the curve (AUC) predicted by ß-C-terminal telopeptide of type I collagen (ß-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum ß- CTX、lactic dehydrogenase、hemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. CONCLUSION: The serum BMIs are correlated with the patients' OS, and ß- CTX can be an independent prognostic factor.

The effect of sarcopenia on outcomes following orthopaedic surgery : a systematic review.

AIMS: Sarcopenia is characterized by a generalized progressive loss of skeletal muscle mass, strength, and physical performance. This systematic review primarily evaluated the effects of sarcopenia on postoperative functional recovery and mortality in patients undergoing orthopaedic surgery, and secondarily assessed the methods used to diagnose and define sarcopenia in the orthopaedic literature. METHODS: A systematic search was conducted in MEDLINE, EMBASE, and Google Scholar databases according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Studies involving sarcopenic patients who underwent defined orthopaedic surgery and recorded postoperative outcomes were included. The quality of the criteria by which a diagnosis of sarcopenia was made was evaluated. The quality of the publication was assessed using Newcastle-Ottawa Scale. RESULTS: A total of 365 studies were identified and screened, 26 full-texts were reviewed, and 19 studies were included in the review. A total of 3,009 patients were included, of whom 2,146 (71%) were female and 863 (29%) were male. The mean age of the patients was 75.1 years (SD 7.1). Five studies included patients who underwent spinal surgery, 13 included hip or knee surgery, and one involved patients who underwent fixation of a distal radial fixation. The mean follow-up was 1.9 years (SD 1.9; 5 days to 5.6 years). There was wide heterogeneity in the measurement tools which were used and the parameters for the diagnosis of sarcopenia in the studies. Sarcopenia was associated with at least one deleterious effect on surgical outcomes in all 19 studies. The postoperative rate of mortality was reported in 11 studies (57.9%) and sarcopenia was associated with poorer survival in 73% (8/11) of these. The outcome was most commonly assessed using the Barthel Index (4/19), and sarcopenic patients recorded lower scores in 75% (3/4) of these. Sarcopenia was defined using the gold-standard three parameters (muscle strength, muscle quantity or quality, and muscle function) in four studies (21%), using two parameters in another four (21%) and one in the remaining 11 (58%). The methodological quality of the studies was moderate to high. CONCLUSION: There is much heterogeneity in the reporting of the parameters which are used for the diagnosis of sarcopenia, and evaluating the outcome of orthopaedic surgery in sarcopenic patients. However, what data exist suggest that sarcopenia impairs recovery and increases postoperative mortality, especially in patients undergoing emergency surgery. Further research is required to develop processes that allow the accurate diagnosis of sarcopenia in orthopaedics, which may facilitate targeted pre- and postoperative interventions that would improve outcomes. Cite this article: Bone Joint J 2022;104-B(3):321-330.

An epidemiological approach to the analysis of cribra orbitalia as an indicator of health status and mortality in medieval and post-medieval London under a model of parasitic infection.

OBJECTIVES: Many individuals living in medieval and post-medieval London suffered issues with sanitation, food insecurity, infectious disease, and widespread exposure to parasites from a multitude of sources, causing increased risk of death for many inhabitants. We examine this stressful environment and its relationship with various demographic and temporal dimensions, using cribra orbitalia (CO) as an indicator of stress, to model an increased risk of dying under the expectations of our proposed parasitic model of infection. MATERIALS AND METHODS: We analyze the relationship between CO and mortality across seven medieval and post-medieval cemeteries from London by the covariates of sex, status, and age-at-death. A survival analysis (Cox regression) and a binomial logit estimated hazard and odds ratios of dying with CO across age-at-death, sex, status, and time-period within single statistical models. In addition, we provide new Bayesian age-at-death estimates for post-medieval samples. RESULTS: The models show the rate of CO decreased over time and age-at-death, regardless of sex or status; post-medieval individuals were ~72% less likely to die with lesions than their medieval counterparts. Further, individuals with CO had ~1% decrease in risk of dying with CO per year of age. DISCUSSION: These results suggest increased mortality risk for those with lesions indicative of anemia (CO), and selective mortality of younger individuals during the medieval period. Despite sex-specific nutritional and occupational hazards, and status-based access to resources, the prevalence of CO was similar across sex and status, which suggests living with parasitic infection that caused anemia was an everyday reality for medieval and post-medieval Londoners.

The doubled burden of diabetic bone disease: hip fracture and post-hip fracture mortality.

OBJECTIVE: Patients with diabetes have an increased risk of osteoporosis and shorter life expectancy. Hip fracture (HF) is the most serious consequence of osteoporosis and is associated with increased mortality risk. We aimed to assess the association of antidiabetic medications with HF and the post-hip fracture mortality risk among diabetic patients ≥50 years. DESIGN: In this nationwide case-control study 53 992 HF cases and 112 144 age-, sex- and region-matched non-hip fracture controls were analyzed. A cohort of hip-fractured diabetic patients were followed-up for an all-cause mortality. METHODS: We defined three groups of diabetic patients based on a prescription of antidiabetic medications: group 1 treated with insulin monotherapy (G1DM), group 2 (G2DM) treated with blood glucose-lowering drugs (BGLD) only, group 3 on a combined BGLD and insulin therapy (G3DM). We applied logistic regression and Cox regression. RESULTS: We identified 2757 G1DM patients, 15 310 G2DM patients, 3775 G3DM patients and 144 294 patients without any antidiabetic treatment. All three groups of diabetic patients had increased odds of HF compared to controls. G1DM patients aged 50-64 years (aOR: 4.80, 95% CI: 3.22-7.17) and G3DM patients (aOR: 1.39, 95% CI: 1.02-1.88) showed the highest HF odds, whereas G2DM patients had 18% decrease in HF odds than their non-diabetic controls (aOR: 0.82, 95% CI: 0.69-0.99). All diabetic patients had increased post-hip fracture mortality risk compared to non-diabetic controls. The highest mortality hazard was observed in G1DM patients, being greater for women than men (HR: 1.71, 95% CI: 1.55-1.89 and HR: 1.44, 95% CI: 1.27-1.64, respectively). CONCLUSIONS: Antidiabetic medications increase the probability of HF. Diabetic patients, who sustained HF have a higher mortality risk than non-diabetic patients.

A paleoepidemiological approach to the osteological paradox: Investigating stress, frailty and resilience through cribra orbitalia.

OBJECTIVES: The Osteological Paradox posits that skeletal lesions may differentially be interpreted as representing resilience or frailty. However, specific consideration of the etiologies and demographic distributions of individual skeletal indicators can inform the criteria on which to differentiate stress, frailty, and resilience. Adopting a life history approach and adaptive plasticity model, this study proposes a framework for the analysis and interpretation of a commonly reported skeletal lesion, cribra orbitalia, which considers the underlying mechanisms of the condition, the clinical and epidemiological literature relating to anemia and malnutrition, and the bioarcheological evidence. MATERIALS AND METHODS: Data were extracted from the European (n = 33 populations) and American (n = 19 populations) modules of the Global History of Health Project. Kaplan-Meier and Cox regression analyses were applied, where time was the age-at-death, and the factor or covariate was presence or absence of cribra orbitalia. RESULTS: Of 37 samples that produced significant results, 21 demonstrated a change in relationship when the subadults were excluded from analysis. When subadults were included, individuals with cribra orbitalia present had statistically significant lower survival time. With subadults excluded, the relationship either became nonsignificant or was reversed. DISCUSSION: We demonstrate that in many cases the inclusion of subadults in analysis impacts upon the apparent mortality associated with cribra orbitalia. Examining cribra orbitalia in children and adults has two separate goals: in children, to determine the prevalence and risk of death associated with active lesions and stress; and in adults, to determine whether childhood health assaults that cause cribra orbitalia are associated with frailty or resilience.

Study of the relationship between vitamin D deficiency, sunlight incidence and skeletal/extra skeletaldiseases

It is estimated that more than 1 billion people worldwide have vitamin D insufficiency or deficiency. Vitamin D participates in bone mineralization, and is therefore important in osteoporosis, osteomalacia and rickets prevention. However, vitamin D deficiency could also be associated with several other pathologies. The present study aimed to investigate the relationships between vitamin D deficiency and vitamin D deficiency-related disorders in patients. In addition, this study aims to verify if countries with low solar incidence have higher extraskeletal disease death rates when compared to countries with high solar incidence. The vitamin D concentrations were obtained from the Heart Hospital database (Natal/Brazil). The relationship between solar incidenceand death rate for vitamin D deficiency-related disorders was verified. Death rate data were extracted from the 'World Life Expectancy' repository and data about solar incidence were obtained from NASA's Surface Meteorology and Solar Energy project. Thesedata were statistically processed with IBM SPSS v23.0 software and R programming language. Our results showed that patients with vitamin D insufficiency/deficiency showed significantly more bone diseases, thyroid diseases, hypercholesterolemy, hypertriglyceridemia, cancers, diabetes, hepatobiliary diseases, and urinary system diseases. Moreover, countries with high solar incidence have low cancer and multiple sclerosis death rates. This work suggests the participation of vitamin D and sunlight incidence inseveral diseases.

Indicators of stress and their association with frailty in the precontact Southwestern United States.

OBJECTIVES: Physiological disturbances in early life have been shown to increase individual mortality risk and impact health in adulthood. This study examines frailty through analysis of lesion status of two commonly collected skeletal indicators of stress (cribra orbitalia [CO] and porotic hyperostosis [PH]) and their association with mortality risk in the precontact U.S. Southwest. Several predictions are addressed: (a) individuals with active skeletal lesions are the frailest; (b) individuals with healed lesions are the least frail; (c) CO lesions, regardless of status, are associated with increased mortality risk. MATERIALS AND METHODS: Odds ratios and Kaplan-Meier survival analysis are used to examine the association between stress indicators and mortality in the U.S. Southwest. This study includes 335 individuals (75 females, 81 males, 20 adults of unknown sex, and 159 juveniles) from precontact New Mexico archaeological sites dating to A.D. 1,000-1,400. RESULTS: Active CO and PH lesions are associated with lower survivorship and greater mortality risk than healed or absent lesions. Only juvenile individuals have active CO and PH lesions, as is expected given their physiology. CO lesions in any state are associated with greater mortality risk and earlier ages of death. DISCUSSION: Individuals with active lesions are the frailest; while individuals with healed lesions are the least frail. CO and PH likely have different etiologies: CO lesions are associated with increased mortality risk and decreased individual longevity. These results indicate that CO's presence suggests a more severe underlying condition than PH lesions alone.

Guideline attainment and morbidity/mortality rates in a large cohort of European haemodialysis patients (EURODOPPS).

BACKGROUND: Haemodialysis patients experience a wide variety of intermediate complications, such as anaemia, hypertension and mineral bone disease (MBD). We aimed to assess the risk of death and hospital admissions as a function of the simultaneous attainment of different guideline targets (for hypertension, anaemia and MBD) in a large European cohort of dialysis patients. METHODS: EURODOPPS is part of the Dialysis Outcomes and Practice Patterns Study (DOPPS) international, prospective cohort study of adult, in-centre haemodialysis patients for whom clinical data are extracted from medical records. In the present analysis, 6317 patients from seven European countries were included between 2009 and 2011. The percentages of patients treated according to the international guidelines on anaemia, hypertension and MBD were determined. The overall degree of guideline attainment was considered to be high if four or all five of the evaluated targets were attained, moderate if two or three targets were attained, and low if fewer than two targets were attained. Fully adjusted multivariate Cox models were used to investigate the relationship of target attainment with mortality and first hospital admission. RESULTS: At baseline, the degree of target attainment was low in 1751 patients (28%), moderate in 3803 (60%) and high in 763 (12%). In the fully adjusted model using time-dependent covariates, low attainment was associated with higher all-cause mortality [hazard ratio (95% confidence interval) = 1.19 (1.05-1.34)] and high attainment was associated with lower all-cause mortality [0.82 (0.68-0.99)]. In a similar model that additionally accounted for death as a competing risk, low and high attainments were not associated with hospital admission. CONCLUSION: In a large international cohort of dialysis patients, we have shown that more stringent application of guidelines is associated with lower mortality.

Bone metastases and skeletal-related events: incidence and prognosis according to histological subtype of lung cancer.

AIM: Estimate the incidence of bone metastases (BM) and skeletal-related events according to the histological subtype of lung cancer and its impact on patient survival. PATIENTS & METHODS: Retrospective cohort study was carried out with patients diagnosed with lung cancer. Cumulative incidence, Kaplan-Meier survival analysis and the risk of death were estimated. RESULTS: In non-small-cell lung cancer (NSCLC), the cumulative incidence of BM during follow-up was 23.8% at 24 months; in small-cell lung cancer, it was 18.5%. The presence of BM in patients with NSCLC was associated with an increased risk of death (hazard ratio: 1.25; 95% CI: 1.04-1.49; p = 0.013). CONCLUSION: This study revealed a high incidence of BM and skeletal-related events. BM was associated with a poor prognosis in NSCLC patients.

Consolidation therapy with the combination of bortezomib and lenalidomide (VR) without dexamethasone in multiple myeloma patients after transplant: Effects on survival and bone outcomes in the absence of bisphosphonates.

Optimizing consolidation treatment in transplant-eligible newly diagnosed multiple myeloma patients in order to improve efficacy and bone-related outcomes is intriguing. We conducted an open-label, prospective study evaluating the efficacy and safety of bortezomib and lenalidomide (VR) consolidation after ASCT, in the absence of dexamethasone and bisphosphonates. Fifty-nine patients, who received bortezomib-based induction, were given 4 cycles of VR starting on day 100 post-ASCT. After ASCT, 58% of patients improved their response status, while following VR consolidation 39% further deepened their response; stringent complete response rates increased to 51% after VR from 24% post-ASCT. VR consolidation resulted in a significant reduction of soluble receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio and sclerostin circulating levels, which was more pronounced among patients achieving very good partial response or better. After a median follow-up of 62 months, no skeletal-related events (SREs) were observed, despite the lack of bisphosphonates administration. The median TTP after ASCT was 37 months, while median overall survival (OS) has not been reached yet; the probability of 4- and 5-year OS was 81% and 64%, respectively. In conclusion, VR consolidation is an effective, dexamethasone- and bisphosphonate-free approach, which offers long OS with improvements on bone metabolism and no SREs.

Pathology and causes of death in stranded humpback whales (Megaptera novaeangliae) from Brazil.

This study describes the pathologic findings of 24 humpback whales (Megaptera novaeangliae) found stranded along the Brazilian coast from 2004 to 2016. Eighteen (75%) animals evaluated were found stranded alive. From these, 13 died naturally on shore and five were euthanized. Six died at sea and were washed ashore. Of the 24, 19 (79.2%) were calves, four (16.7%) were juveniles, and one (4.2%) was an adult. The most probable cause of stranding and/or death (CSD) was determined in 23/24 (95.8%) individuals. In calves, CSD included neonatal respiratory distress (13/19; 68.4%), infectious disease (septicemia, omphaloarteritis and urachocystitis; 3/19; 15.8%), trauma of unknown origin (2/19; 10.5%), and vehicular trauma (vessel strike; 1/19; 5.3%). In juveniles and adult individuals, CSD was: emaciation (2/5; 40%), sunlight-thermal burn shock (1/5; 20%); and discospondylitis (1/5; 20%). In one juvenile, the CSD was undetermined (1/5; 20%). This study integrates novel findings and published case reports to delineate the pathology of a South-western Atlantic population of humpback whales. This foundation will aid in the assessment of the population health and establish a baseline for development of conservation policies.

Outcome After Radiation Therapy for Langerhans Cell Histiocytosis Is Dependent on Site of Involvement.

PURPOSE: To characterize the efficacy and safety of radiation therapy in a contemporary Langerhans cell histiocytosis (LCH) cohort and to explore whether there are sites at higher risk for local recurrence. PATIENTS AND METHODS: Between 1995 and 2015 we identified 39 consecutive LCH patients who were treated primarily with radiation therapy. Patients were staged by single/multisystem involvement and established risk organ criteria. In 46 irradiated lesions, clinical and radiologic responses were evaluated at multiple time points after radiation therapy. Patient demographics, treatment, and local failure were compared by site of lesion. RESULTS: Median age at radiation therapy was 35 years (range, 1.5-67 years). Twelve patients had multisystem involvement, and of those, 5 patients had disease in organs considered to be high risk. The following sites were irradiated: bone (31), brain (6), skin (3), lymph node (3), thyroid (2), and nasopharynx (1). Median dose was 11.4 Gy (range, 7.5-50.4 Gy). At a median follow-up of 45 months (range, 6-199 months), local recurrence or progression was noted in 5 of 46 lesions (11%). There were no local failures of the 31 bone lesions evaluated, whereas the 3-year freedom from local failure in the 15 non-bone lesions was 63% (95% confidence interval 32-83%; P=.0008). Local failures occurred in 2 of 3 skin lesions, in 2 of 6 brain lesions, and 1 of 3 lymph node lesions. Deaths were recorded in 5 of 39 patients (13%), all of whom were adults with multisystem disease. CONCLUSION: Radiation therapy is a safe and effective measure for providing local control of LCH involving the bone. Whereas bone lesions are well controlled with low doses of radiation, disease in other tissues, such as the skin and brain, may require higher doses of radiation or additional treatment modalities.

Bisphosphonates in multiple myeloma: an updated network meta-analysis.

BACKGROUND: Bisphosphonates are specific inhibitors of osteoclastic activity and are used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be effective in reducing vertebral fractures and pain, their role in improving overall survival (OS) remains unclear. This is an update of a Cochrane review first published in 2002 and previously updated in 2010 and 2012. OBJECTIVES: To assess the evidence related to benefits and harms associated with use of various types of bisphosphonates (aminobisphosphonates versus non-aminobisphosphonates) in the management of patients with MM. Our primary objective was to determine whether adding bisphosphonates to standard therapy in MM improves OS and progression-free survival (PFS), and decreases skeletal-related morbidity. Our secondary objectives were to determine the effects of bisphosphonates on pain, quality of life, incidence of hypercalcemia, incidence of bisphosphonate-related gastrointestinal toxicities, osteonecrosis of jaw (ONJ) and hypocalcemia. SEARCH METHODS: We searched MEDLINE, Embase (September 2011 to July 2017) and the CENTRAL (2017, Issue 7) to identify all randomized controlled trial (RCT) in MM up to July 2017 using a combination of text and MeSH terms. SELECTION CRITERIA: Any randomized controlled trial (RCT) comparing bisphosphonates versus placebo/no treatment/bisphosphonates and observational studies or case reports examining bisphosphonate-related ONJ in patients with MM were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors extracted the data. Data were pooled and reported as hazard ratio (HR) or risk ratio (RR) using a random-effects model. We used meta-regression to explore statistical heterogeneity. Network meta-analysis using Bayesian approach was conducted. MAIN RESULTS: In this update, we included four new studies (601 participants), resulting in a total of 24 included studies.Twenty RCTs compared bisphosphonates with either placebo or no treatment and four RCTs involved another bisphosphonate as a comparator. The 24 included RCTs enrolled 7293 participants. Pooled results showed that there was moderate-quality evidence of a reduction in mortality with on OS from 41% to 31%, but the confidence interval is consistent with a larger reduction and small increase in mortality compared with placebo or no treatment (HR 0.90, 95% CI 0.76 to 1.07; 14 studies; 2706 participants). There was substantial heterogeneity among the included RCTs (I2 = 65%) for OS. To explain this heterogeneity we performed a meta-regression assessing the relationship between bisphosphonate potency and improvement in OS, which found an OS benefit with zoledronate but limited evidence of an effect on PFS. This provided a further rationale for performing a network meta-analyses of the various types of bisphosphonates that were not compared head-to-head in RCTs. Results from network meta-analyses showed evidence of a benefit for OS with zoledronate compared with etidronate (HR 0.56, 95% CI 0.29 to 0.87) and placebo (HR 0.67, 95% CI 0.46 to 0.91). However, there was no evidence for a difference between zoledronate and other bisphosphonates.The effect of bisphosphonates on disease progression (PFS) is uncertain. Based on the HR of 0.75 (95% CI 0.57 to 1.00; seven studies; 908 participants), 47% participants would experience disease progression without treatment compared with between 30% and 47% with bisphosphonates (low-quality evidence). There is probably a similar risk of non-vertebral fractures between treatment groups (RR 1.03, 95% CI 0.68 to 1.56; six studies; 1389 participants; moderate-quality evidence). Pooled analysis demonstrated evidence for a difference favoring bisphosphonates compared with placebo or no treatment on prevention of pathological vertebral fractures (RR 0.74, 95% CI 0.62 to 0.89; seven studies; 1116 participants; moderate-quality evidence) and skeletal-related events (SREs) (RR 0.74, 95% CI 0.63 to 0.88; 10 studies; 2141 participants; moderate-quality evidence). The evidence for less pain with bisphosphonates was of very low quality (RR 0.75, 95% CI 0.60 to 0.95; eight studies; 1281 participants).Bisphosphonates may increase ONJ compared with placebo but the confidence interval is very wide (RR 4.61, 95% CI 0.99 to 21.35; P = 0.05; six studies; 1284 participants; low-quality evidence). The results from the network meta-analysis did not show any evidence for a difference in the incidence of ONJ (eight RCTs, 3746 participants) between bisphosphonates. Data from nine observational studies (1400 participants) reported an incidence of 5% to 51% with combination of pamidronate and zoledronate, 3% to 11% with zoledronate alone, and 0% to 18% with pamidronate alone.The pooled results showed no evidence for a difference in increase in frequency of gastrointestinal symptoms with the use of bisphosphonates compared with placebo or no treatment (RR 1.23, 95% CI 0.95 to 1.59; seven studies; 1829 participants; low-quality evidence).The pooled results showed no evidence for a difference in increase in frequency of hypocalcemia with the use of bisphosphonates compared with placebo or no treatment (RR 2.19, 95% CI 0.49 to 9.74; three studies; 1090 participants; low-quality evidence). The results from network meta-analysis did not show any evidence for differences in the incidence of hypocalcemia, renal dysfunction and gastrointestinal toxicity between the bisphosphonates used. AUTHORS' CONCLUSIONS: Use of bisphosphonates in participants with MM reduces pathological vertebral fractures, SREs and pain. Bisphosphonates were associated with an increased risk of developing ONJ. For every 1000 participants treated with bisphosphonates, about one patient will suffer from the ONJ. We found no evidence of superiority of any specific aminobisphosphonate (zoledronate, pamidronate or ibandronate) or non-aminobisphosphonate (etidronate or clodronate) for any outcome. However, zoledronate was found to be better than placebo and first-generation bisposphonate (etidronate) in pooled direct and indirect analyses for improving OS and other outcomes such as vertebral fractures. Direct head-to-head trials of the second-generation bisphosphonates are needed to settle the issue if zoledronate is truly the most efficacious bisphosphonate currently used in practice.

Long-Term Follow-Up of Primary Medical Versus Surgical Treatment of Prolactinomas in Men: Effects on Hyperprolactinemia, Hypogonadism, and Bone Health.

OBJECTIVE: In men with prolactinomas, impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. Although dopamine agonists (DAs) are the first-line approach in prolactinomas, surgery can be considered in selected cases. In this study, we aimed to investigate the long-term control of hyperprolactinemia, hypogonadism, and bone health comparing primary medical and surgical therapy in men who had not had prior DA treatment. METHODS: This is a retrospective case-note study of 44 consecutive men with prolactinomas and no prior DAs managed in a single tertiary referral center. Clinical, biochemical, and radiologic response to the first-line approach were analyzed in the 2 cohorts. RESULTS: Mean age at diagnosis was 47 years (range, 22-78 years). The prevalence of hypogonadism was 86%, and 27% of patients had pathologic bone density at baseline. The primary therapeutic strategy was surgery for 34% and DAs for 66% of patients. Median long-term follow-up was 63 months (range, 17-238 months). Long-term control of hyperprolactinemia required DAs in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (P = 0.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathologic bone density was 37% at last follow-up, with no differences between the 2 therapeutic cohorts (P = 0.48). CONCLUSIONS: Despite control of hyperprolactinemia and hypogonadism in most patients independent of the primary treatment modality, the prevalence of impaired bone health status remains high, and osteodensitometry should be recommended.

Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.

BACKGROUND: Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. METHODS: Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. RESULTS: From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. CONCLUSIONS: In hemodialysis patients, FGF23 is a predictor of all-cause and cardiovascular mortality, whereas the predictive value of OPG is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients.

Morbimortality in adult patients with septic arthritis: a three-year hospital-based study.

BACKGROUND: The objective of this ambispective study was to determine outcomes and associated factors for adult patients with confirmed septic arthritis (SA). METHODS: All adult patients admitted to Amiens University Hospital between November 2010 and December 2013 with confirmed SA were included in the study. Patients with prosthetic joint infections were excluded. A statistical analysis was performed in order to identify risk factors associated with a poor outcome (including mortality directly attributable to SA). RESULTS: A total of 109 patients (mean ± SD age: 60.1 ± 20.1; 74 male/35 females) were diagnosed with SA during the study period. The most commonly involved sites were the small joints (n = 34, 31.2 %) and the knee (n = 25, 22.9 %). The most frequent concomitant conditions were cardiovascular disease (n = 45, 41.3 %) and rheumatic disease (n = 39, 35.8 %). One hundred patients (91.7 %) had a positive microbiological culture test, with Staphylococcus aureus as the most commonly detected pathogen (n = 59, 54.1 %). Mortality directly attributable to SA was relatively infrequent (n = 6, 5.6 %) and occurred soon after the onset of SA (median [range]: 24 days [1-42]). Major risk factors associated with death directly attributable to SA were older age (p = 0.023), high C-reactive protein levels (p = 0.002), diabetes mellitus (p = 0.028), rheumatoid arthritis and other inflammatory rheumatic diseases (p = 0.021), confusion on admission (p = 0.012), bacteraemia (p = 0.015), a low creatinine clearance rate (p = 0.009) and the presence of leg ulcers/eschars (p = 0.003). The median duration of follow-up (in patients who survived for more than 6 months) was 17 months [6-43]. The proportion of poor functional outcomes was high (31.8 %). Major risk factors associated with a poor functional outcome were older age (0.049), hip joint involvement (p = 0.003), the presence of leg ulcers/eschars (p = 0.012), longer time to presentation (0.034) and a low creatinine clearance rate (p = 0.013). CONCLUSIONS: In a university hospital setting, SA is still associated with high morbidity and mortality rates.

Total Hip Arthroplasty With an Uncemented Tapered Femoral Component in Patients Younger Than 50 Years of Age: A Minimum 20-Year Follow-Up Study.

BACKGROUND: Previously, we reported the mean 16-year results of primary uncemented total hip arthroplasty using a tapered femoral component in patients <50 years. The purpose of this study was to update our previous report using the Taperloc femoral component in young patients who had been followed for a minimum of 20 years postoperatively. METHODS: Between 1983 and 1990, 108 consecutive uncemented total hip arthroplasties were performed in 91 patients of age <50 years, with use of the Taperloc femoral component. Every patient was followed for a minimum of 20 years after surgery or until death. At a mean of 25 (range, 20-29 years) postoperatively, 76 patients (91 hips) were living. The Harris Hip Score, radiographic results, complications, and Kaplan-Meier survivorship were evaluated. RESULTS: In the entire cohort of 108 hips, 9 femoral components (8%) have been revised, none for aseptic loosening. Five well-fixed stems were removed during acetabular revision, 3 stems were revised for infection, and 1 stem was exchanged because of a peroneal nerve palsy. Distal femoral osteolysis was identified around 1 hip. With failure defined as stem removal for any reason, implant survival was 90% (CI = 82-95) at 29 years. With failure defined as stem removal for aseptic loosening, implant survival was 100% at 29 years. CONCLUSION: Primary total hip arthroplasty with the Taperloc femoral component in young patients was associated with a high rate of survival at 29 years.

Management and Outcome of Patients With Langerhans Cell Histiocytosis and Single-Bone CNS-Risk Lesions: A Multi-Institutional Retrospective Study.

BACKGROUND: Children with Langerhans cell histiocytosis (LCH) and single-bone CNS-risk lesions have been reported to be at increased risk of diabetes insipidus (DI), central nervous system neurodegeneration (CNS-ND), and recurrence of disease. However, it is unknown whether the addition of chemotherapy or radiotherapy changes outcomes in these patients. METHODS: Ten pediatric institutions across North America and Europe contributed data of their patients with LCH and single-bone CNS-risk lesions. Clinical information on age, sex, specific craniofacial site involvement, and intracranial extension at diagnosis, therapy, and disease course was collected for all eligible patients. RESULTS: The final analysis included 93 eligible children who were either treated with systemic therapy (chemotherapy, chemo-radiotherapy, or radiotherapy) or local therapy (biopsy, curettage, and/or intralesional steroids). Fifty-nine patients had systemic and 34 had local therapy. The 5-year event-free survival (EFS) and overall survival (OS) were 80 ± 5% and 98 ± 2% in the systemic therapy group versus 85 ± 6% and 95 ± 5% in the local therapy group. There was no statistically significant difference between either group with regard to EFS (P = 0.26) and OS (P = 0.78). On multivariable analysis, there was no significant difference among the two treatment groups after adjusting for site and intracranial soft tissue extension, nor any trend favoring systemic therapy (HR = 2.26, 95% CI = 0.77-6.70; P = 0.14). CONCLUSION: Systemic therapy may not reduce the risk of recurrence or late sequelae in children with LCH and single-bone CNS-risk lesions as compared to local treatment.

Zoledronic acid as compared with observation in multiple myeloma patients at biochemical relapse: results of the randomized AZABACHE Spanish trial.

This study analyzed the anti-myeloma effect of zoledronic acid monotherapy by investigating patients at the time of asymptomatic biochemical relapse. One hundred patients were randomized to receive either zoledronic acid (4 mg iv/4 weeks, 12 doses) (n=51) or not (n=49). Experimental and control groups were well balanced for disease and prognostic features. Zoledronic acid did not show an antitumor effect according to changes in M-component. However, there were fewer symptomatic progressions in the experimental group than in the control group (34 versus 41, respectively; P=0.05) resulting in a median time to symptoms of 16 versus 10 months (P=0.161). The median time to next therapy was also slightly longer for the treated group than the untreated, control group (13.4 versus 10.1 months), although the difference was not statistically significant (P=0.360). The pattern of relapses was different for treated versus control patients: progressive bone disease (8 versus 20), anemia (24 versus 18), renal dysfunction (1 versus 2), and plasmacytomas (1 versus 1, respectively). This concurred with fewer skeletal-related events in the treated group than in the control group (2 versus 14), with a projected 4-year event proportion of 6% versus 40% (P<0.001). In summary, zoledronic acid monotherapy does not show an antitumor effect on biochemical relapses in multiple myeloma, but does reduce the risk of progression with symptomatic bone disease and skeletal complications. This trial was registered in the ClinicalTrials.gov database with code NCT01087008.

Effects of Radiotherapy in the treatment of multiple myeloma: a retrospective analysis of a Single Institution.

BACKGROUND: Palliative irradiation of osteolytic lesions is a considerable component in the treatment for patients with multiple myeloma. In this study, we analyzed the efficacy of irradiation in these patients. PATIENTS AND METHODS: We retrospectively analyzed 153 patients with multiple myeloma who were admitted to our department between 1989 and 2013. According to the staging system of Durie & Salmon 116 patients were classified as stage III. 107/153 patients were treated with radiotherapy of at least one and up to 6 bony lesions at different times. In order to evaluate the effect of local radiotherapy on pain relief and bone recalcification a uni- and multivariate analysis was performed using a binary logistic regression model to correct for multiple measurements. Complete information on dose, fractionation and volume of radiotherapy was available from 81 patients treated in 136 target volumes for pain relief, and from 69 patients treated in 108 target volumes for recalcification. Total radiation doses varied between 8 Gy to 50 Gy (median dose 25 Gy in 2.5 Gy fractions, 5 times a week). RESULTS: Radiotherapy resulted in complete local pain relief in 31% and partial local pain relief in 54% of the patients. In the univariate analysis, higher total radiation doses (p = 0.023) and higher age (p = 0.014) at the time of radiotherapy were significantly associated with a higher likelihood of pain relief, whereas no significant association was detected for concurrent systemic treatment, type and stage of myeloma and location of bone lesions. The same variables were independent predictors for pain relief in the multivariate analysis. Recalcification was observed in 48% of irradiated bone lesions. In the uni- and multivariate analysis higher radiation doses were significantly associated (p = 0.048) with an increased likelihood of recalcification. Side effects of radiotherapy were generally mild. CONCLUSIONS: Higher total biological radiation doses were associated with better pain relief and recalcification in this retrospective evaluation of multiple myeloma patients. In addition, in the elderly the therapeutic measures appear to develop a better analgesic effect.