Melton, L. Joseph

Abstract Abstract 1861 Idiopathic Bence Jones Proteinuria (Smoldering Monoclonal Light-Chain Proteinuria), first reported in 1982, is an asymptomatic plasma cell proliferative disorder associated with an elevated risk of progression to symptomatic MM or amyloidosis (AL). We defined it as the presence of a monoclonal light chain in the urine ≥200 mg/24h, absence of an intact immunoglobulin M protein (IGH expression) in the serum and no evidence of MM, AL or other related plasma cell proliferative disorders. Following approval by our Institutional Review Board, we searched a computerized database and reviewed the records of all patients seen at Mayo Clinic within 30 days of the recognition of a monoclonal light chain (Bence Jones protein) in the urine from January 1, 1960 through June 30, 2004. Patients with end-organ damage at diagnosis resulting from the plasma cell proliferative disorder (including MM or AL), or who had received chemotherapy or had a nephrotic syndrome were excluded. Follow-up included review of each patient's medical record at Mayo Clinic, as well as review of death certificates for patients who died. Patients were sent letters of inquiry if they had not visited Mayo Clinic in the preceding year. The risks of progression to MM and AL were compared to those expected on the basis of Surveillance, Epidemiology and End Results (SEER) rates for MM in Iowa and the incidence of AL in Olmsted County, Minnesota. One-hundred and one patients fulfilled the criteria for diagnosis during the 44-year period (1960–2004). The median age at diagnosis was 67 years (range 18–90 years), and only 2% were < 40 years old. Seventy-three percent were male. The urine M protein ranged from 200 mg/24h to 4.7 g/24h (median value, 500 mg/24h); 29% had > 1 g/24h. Kappa light chain accounted for 50% while the remaining 50% were lambda. Fifty-seven (56%) had a monoclonal light chain in the serum on immunofixation. Concentrations of uninvolved (normal, polyclonal or background) immunoglobulins were reduced in 62%. Eighty-eight percent of patients died during follow-up. During 900 person years of follow-up, 29 patients developed symptomatic MM (relative risk, 140.3; 95% CI, 93.9–201.5) and an additional 9 patients developed AL (relative risk, 104.4; 95% CI, 47.8–198.4). Four patients had both multiple myeloma and AL amyloidosis. The cumulative probability of progression to active MM or AL was 19% at 5 years, 31% at 10 years and 42% at 15 years. The factors associated with progression to MM or AL included size of urine M protein, percentage of bone marrow plasma cells, serum free light chain ratio < 1/100 or > 100, serum creatinine and reduction of all 3 uninvolved immunoglobulins. We conclude that patients with Idiopathic Bence Jones Proteinuria (Smoldering Monoclonal Light-Chain Proteinuria) are at risk for the development of MM or AL and must be followed indefinitely. Disclosures: No relevant conflicts of interest to declare.

Ice hockey is a team sport that has recently grown in popularity not only in the United States but also in Canada and Europe. With this increase in popularity has come a growing concern about the number and severity of injuries. The world literature on the biomechanics and physiology of ice hockey was reviewed in an attempt to evaluate the forces and mechanisms involved in the game. The influence of rule and equipment changes on injury patterns was particularly studied. Several studies on the epidemiology of injuries, providing data on the types of injuries and the mechanisms of those injuries, were analyzed to determine the conclusions that could be supported and those that require further study. Possible changes in the patterns and types of injury are outlined.

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous.

Key Points VTE recurrence risk in patients with cancer can be stratified by cancer type, stage, stage progression, and presence of leg paresis. Patients with cancer at high VTE recurrence risk should be considered for secondary prophylaxis.

ABSTRACT Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone “quality”). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50–80 years) including 30 patients diagnosed with T2D for &gt;10 years and 30 age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed from high-resolution peripheral quantitative computed tomography (HRpQCT) images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (−11.7%; p &lt; 0.001); following adjustment for body mass index (BMI) (−10.5%; p &lt; 0.001); and following additional adjustment for age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (−9.2%; p = 0.022). By contrast, after adjustment for confounding by BMI, T2D patients had bone microarchitecture and BMD that were not significantly different than controls; however, radial cortical porosity tended to be higher in the T2D patients. In addition, patients with T2D had significantly reduced serum markers of bone turnover (all p &lt; 0.001) compared to controls. Of note, in patients with T2D, the average glycated hemoglobin level over the previous 10 years was negatively correlated with BMS (r = −0.41; p = 0.026). In conclusion, these findings represent the first demonstration of compromised BMS in patients with T2D. Furthermore, our results confirm previous studies demonstrating low bone turnover in patients with T2D and highlight the potential detrimental effects of prolonged hyperglycemia on bone quality. Thus, the skeleton needs to be recognized as another important target tissue subject to diabetic complications. © 2014 American Society for Bone and Mineral Research.

ABSTRACT Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20–105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m2) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m2, the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m2 was 0.87 (95% confidence interval [CI], 0.85–0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09–1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored. © 2014 American Society for Bone and Mineral Research.

ABSTRACT Distal forearm fractures are among the most common fractures during childhood, but it remains unclear whether they predict an increased fracture risk later in life. We studied a population-based cohort of 1776 children ≤18 years of age, from Olmsted County, MN, USA, who had a distal forearm fracture in 1935–1992. Incident fractures occurring at age ≥35 years were identified through review of complete medical records using the linkage system of the Rochester Epidemiology Project. Observed nonpathologic fractures resulting from no more than moderate trauma (fragility fractures) were compared with expected numbers estimated from fracture site–specific incidence rates, based on age, sex, and calendar year, for Olmsted County (standardized incidence ratios [SIR]). In 1086 boys (mean ± SD age; 11 ± 4 years) and 690 girls (10 ± 4 years) followed for 27,292 person-years after the age of 35 years, subsequent fragility fractures were observed in 144 (13%) men and 74 (11%) women. There was an increased risk for future fragility fractures in boys who had a distal forearm fracture (SIR, 1.9; 95% CI, 1.6–2.3) but not girls (SIR, 1.0; 95% CI, 0.8–1.2). Fragility fractures at both major osteoporotic (hip, spine, wrist, and shoulder) sites (SIR, 2.6; 95% CI, 2.1–3.3) and remaining sites (SIR, 1.7; 95% CI, 1.3–2.0) were increased in men, irrespective of age at distal forearm fracture as boys. A distal forearm fracture in boys, but not girls, is associated with an increased risk for fragility fractures as older adults. It is necessary to determine whether the increased fractures observed in men is due to persistent deficits of bone strength, continued high fracture risk activity, or both. Until then, men should be asked about a childhood distal forearm fracture and, if so, warrant further screening and counseling on measures to optimize bone health and prevent fractures.