Changes to osteoporosis prevalence according to method of risk assessment.

The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk. INTRODUCTION: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. MATERIALS AND METHODS: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. RESULTS: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. CONCLUSIONS: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.     

The frequency of vitamin D deficiency in adults with Crohn's disease.

BACKGROUND: Vitamin D deficiency is a putative, pathogenic cofactor in the increase in osteopenia and osteoporosis seen in patients with Crohn's disease. OBJECTIVE: To determine the frequency of low serum 25-hydroxy-vitamin D3 (25-OHD) levels and the associated alterations in bone mineral density in a cohort of adults with Crohn's disease. METHODS: 25-OHD levels were determined in 242 consecutive patients with Crohn's disease seen in two tertiary inflammatory bowel disease referral centres. Bone mineral density was assessed by dual energy x-ray absorptiometry. RESULTS: Nineteen (8%) patients exhibited vitamin D deficiency (25-OHD less than 25 nmol/L) and 52 (22%) patients exhibited vitamin D insufficiency (25-OHD less than 40 nmol/L). Mean T-scores at the lumbar spine, femoral neck, total hip and ultradistal radius in the group with low 25-OHD did not differ from those of the normal 25-OHD group. Serum alkaline phosphatase and parathyroid hormone levels were higher in the low 25-OHD group than in the normal group. Decreased red blood cell (RBC) folate predicted low 25-OHD in male patients, while smoking, RBC folate and serum iron predicted low 25-OHD in female patients. The rate of low 25-OHD deficiency in the winter was significantly higher than that in the summer (11.9% versus 2.8%, respectively). CONCLUSION: Vitamin D-deficient Crohn's disease patients exhibit biochemical evidence of metabolic bone disease, without detectable differences in bone mineral density. Sunlight exposure, nutrition and smoking status were predictors of vitamin D deficiency in this patient cohort.     

The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches

Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n = 343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <−1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8–15) with 46% of IVF (95% CI 30–61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57–85) but would require radiographs in 37% of children (95% CI 32–42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83–91), the greatest overall accuracy at 82% (95% CI 78–86), and the lowest radiography rate at 17% (95% CI 14–22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67–92), but required radiographs in 65% (95% CI 60–70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR).     

The relationships among height,penile length,and foot size

To determine whether "folk myths" regarding the relationships of penile size to body height and foot size have any basis in fact, 63 normally virilized men were studied. Height and stretched penile length were measured; shoe size was recorded and converted to foot length. Penile length was found to be statistically related to both body height and foot length, but with weak correlation coefficients. Height and foot size would not serve as practical estimators of penis length.     

Phosphorylation of factor Va and factor VIIIa by activated platelets

Platelet activation leads to the incorporation of 32[PO4(2-)] into bovine coagulation factor Va and recombinant human factor VIII. In the presence of the soluble fraction from thrombin-activated platelets and (gamma-32P) adenosine triphosphate, radioactivity is incorporated exclusively into the M(r) = 94,000 heavy chain (H94) of factor Va and into the M(r) = 210,000 to 90,000 heavy chains as well into the M(r) = 80,000 light chain of factor VIII. Proteolysis of the purified phosphorylated M(r) = 94,000 factor Va heavy chain by activated protein C (APC) gave products of M(r) = 70,000, 24,000, and 20,000. Only the intermediate M(r) = 24,000 fragment contained radioactivity. Because the difference between the M(r) = 24,000 and M(r) = 20,000 fragments is located on the COOH-terminal end of the bovine heavy chain, phosphorylation of H94 must occur within the M(r) = 4,000 peptide derived from the carboxyl-terminal end of H94 (residues 663 through 713). Exposure of the radioactive factor VIII molecule to thrombin ultimately resulted in a nonradioactive light chain and an M(r) = 24,000 radioactive fragment that corresponds to the carboxyl-terminal segment of the A1 domain of factor VIII. Based on the known sequence of human factor VIII, phosphorylation of factor VIII by the platelet kinase probably occurs within the acidic regions 337 through 372 and 1649 through 1689 of the procofactor. These acidic regions are highly homologous to sequences known to be phosphorylated by casein kinase II. Results obtained using purified casein kinase II gave a maximum observed stoichiometry of 0.6 mol of 32[PO4(2-)]/mol of factor Va heavy chain and 0.35 mol of 32[PO4(2-)]/mol of factor VIII. Phosphoamino acid analysis of phosphorylated factor Va by casein kinase II or by the platelet kinase showed only the presence of phosphoserine while phosphoamino acid analysis of phosphorylated factor VIII by casein kinase II showed the presence of phosphothreonine as well as small amounts of phosphoserine. The platelet kinase responsible for the phosphorylation of the two cofactors was found to be inhibited by several synthetic protein kinase inhibitors. Finally, partially phosphorylated factor Va was found to be more sensitive to APC inactivation than its native counterpart. Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II- like kinase may downregulate the activity of the two cofactors.     

Factor V Quebec revisited

Factor V Quebec has been described as a bleeding disorder that exhibits an autosomal dominant inheritance pattern and presents severe bleeding after trauma. Two members of a fourth-generation (IV.13 and IV.15) Canadian family have been studied in detail and are the subject of this report. Their clinical presentations and histories have been described previously (Tracy et al: J Clin Invest 74:1221, 1984). Persistent abnormalities include mild thrombocytopenia and defective platelet factor V. Plasma factor V is present at near normal concentration and is fully functional. Thus, the bleeding diathesis appears to reflect the absence of platelet factor V activity. The recent report (Hayward et al: Blood 84:110a, 1994 [suppl, abstr]) of multimerin deficiency in these individuals led us to reevaluate these patients. Western blot analyses of platelet lysates developed with a variety of monoclonal antibodies show that the alpha-granule proteins, fibrinogen, von Willebrand factor, factor V and osteonectin are decreased in concentration and significantly degraded in the platelets of these patients. Thrombospondin, while not degraded, is substantially decreased. In contrast, platelet factor 4 and beta-thromboglobulin do not appear to be affected. These observations suggest that the alpha- granules are correctly assembled but the contents are subsequently subjected to proteolytic degradation. The results indicate that factor V Quebec disorder is probably associated with a generalized defect that leads to degradation of most proteins of the alpha-granules.