In Paget's disease of bone, the normal lamellar bone is replaced by a woven structure with an irregular arrangement of collagen fibers. In this study, we investigated whether the degree of beta-isomerization within C-telopeptide of alpha 1 chain of type I collagen was altered in Paget's disease compared with other bone diseases with no alteration of bone structure. In Paget's disease (n = 26), but not in patients with primary hyperparathyroidism (n = 6) or hyperthyroidism (n = 17), the urinary excretion of nonisomerized (alpha) fragments derived from degradation of type I collagen C-telopeptide (CTX) was markedly increased compared with beta-isomerized CTX (+ 13-fold vs. + 3.5-fold over controls) resulting in an urinary alpha CTX/beta CTX ratio 3-fold higher than in controls (2.6 +/- 1.0 vs. 0.8 +/- 0.3, p < 0.001). In five pagetic patients in complete remission, as demonstrated by normal total alkaline phosphatase activity, the alpha CTX/beta CTX ratio was normal. The immunohistochemistry of normal and pagetic human bone sections showed a preferential distribution of alpha CTX within woven structure, while lamellar bone was intensely stained with an anti-beta CTX antibody, suggesting a lower degree of beta-isomerization of type I collagen in the woven pagetic bone. In collagenase digest of human bone specimens, we found a lower proportion of beta-isomerized type I collagen molecules in pagetic bone (40% of beta CTX) than in normal bone taken from trabecular (68%) and cortical compartments (71%). In conclusion, we found that in Paget's disease the alpha CTX/beta CTX ratio in bone and in urine is markedly increased. This altered beta isomerization can be accurately detected in vivo by measuring urinary degradation products arising from bone resorption.

Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age +/- SD: 60.2 +/- 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: -2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCL (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p < 0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p < 0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p < 0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p < 0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.

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Porokeratoma (porokeratotic acanthoma) is a very recently described tumor-like acanthoma with features of porokeratosis (cornoid lamellation). We report herein a new case of this poorly known lesion that was studied immunohistochemically and discuss briefly its relationship with porokeratosis.

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A patient-centered care program with a dedicated case manager can significantly improve post-fracture BMD investigation.

Distinguishing between macrophage activation syndrome (MAS) and a simple flare of Still’s disease (SD) may be challenging. We sought to clarify the clinical features and outcome of MAS in SD and to explore predictive factors of MAS development. Demographic and clinical data, treatments, and outcomes were recorded in a cohort of 206 SD patients. SD patients with and without MAS were compared. To explore predictive factors for the development of MAS, patients were compared at the time of SD diagnosis. Twenty (9.7%) patients experienced MAS, which was inaugural in 12 cases. Patients with MAS were more likely to have hepatomegaly (OR, 3.71; 95% CI, 1.14–11.2; p = 0.03) and neurological symptoms (OR, 4.43; 95% CI, 1.08–15.3; p = 0.04) than patients without MAS. Cytopenias, abnormal liver tests, and coagulation disorders were significantly more frequent in patients with MAS; lactate dehydrogenase and serum ferritin levels were significantly higher. An optimized threshold of 3500 μg/L for serum ferritin yielded a sensitivity (Se) of 85% and a negative predictive value (NPV) of 97% for identifying patients with/without MAS. Survival analysis showed that a high ferritin level at the time of SD diagnosis was predictive of MAS development (p < 0.001). Specific factors, including neurological symptoms, cytopenias, elevated LDH, and coagulopathy, may contribute to the early detection of MAS. Extreme hyperferritinemia at the onset of SD is a prognostic factor for the development of MAS.