Methylation of Bone SOST,Its mRNA,and Serum Sclerostin Levels Correlate Strongly With Fracture Risk in Postmenopausal Women

Inhibition of sclerostin, a glycoprotein secreted by osteocytes, offers a new therapeutic paradigm for treatment of osteoporosis (OP) through its critical role as Wnt/catenin signaling regulator. This study describes the epigenetic regulation of SOST expression in bone biopsies of postmenopausal women. We correlated serum sclerostin to bone mineral density (BMD), fractures, and bone remodeling parameters, and related these findings to epigenetic and genetic disease mechanisms. Serum sclerostin and bone remodeling biomarkers were measured in two postmenopausal groups: healthy (BMD T‐score > –1) and established OP (BMD T‐score < –2.5, with at least one low‐energy fracture). Bone specimens were used to analyze SOST mRNAs, single nucleotide polymorphisms (SNPs), and DNA methylation changes. The SOST gene promoter region showed increased CpG methylation in OP patients (n = 4) compared to age and body mass index (BMI) balanced controls (n = 4) (80.5% versus 63.2%, p = 0.0001) with replication in independent cohorts (n = 27 and n = 36, respectively). Serum sclerostin and bone SOST mRNA expression correlated positively with age‐adjusted and BMI‐adjusted total hip BMD (r = 0.47 and r = 0.43, respectively; both p < 0.0005), and inversely to serum bone turnover markers. Five SNPs, one of which replicates in an independent population‐based genomewide association study (GWAS), showed association with serum sclerostin or SOST mRNA levels under an additive model (p = 0.0016 to 0.0079). Genetic and epigenetic changes in SOST influence its bone mRNA expression and serum sclerostin levels in postmenopausal women. The observations suggest that increased SOST promoter methylation seen in OP is a compensatory counteracting mechanism, which lowers serum sclerostin concentrations and reduces inhibition of Wnt signaling in an attempt to promote bone formation. © 2014 American Society for Bone and Mineral Research.     

Chondroblastoma of the hands and feet

Objective To review the imaging findings, age and gender distribution of chondroblastoma of the hands and feet.Design and patients Twenty-five cases of pathologically proven chondroblastoma of the hands and feet were reviewed. Available imaging modalities included radiographs (n=24), CT (n=3), MRI (n=5), and radionuclide bone scintigraphy (n=1). The following imaging features for each case were tabulated: location, presence of sclerotic margin, calcification, expansion, presence of fluid/fluid levels on cross-sectional imaging and surrounding edema on MRI. The images were evaluated for skeletal maturity using closure of the physeal plate in the region as a standard.Results The average age at time of diagnosis was 23 years (range 7–57 years). Eighty-four percent (n=21) of the patients were skeletally mature. Males (20 of 25) outnumbered females by a ratio of 5:1. The bones of the foot accounted for 22 cases: calcaneus (n=8), talus (n=8), metatarsals (n=3), and the cuboid (n=3). The bones of the hand accounted for three cases: phalanx (n=1), triquetrum (n=1), and a metacarpal (n=1). Radiographically all lesions were osteolytic with identifiable calcification in 54% (13 of 24). Fluid/fluid levels were seen in four of five cases on MRI. Edema on MR images was seen in 40% (2 of 5). The size of the lesions ranged from 2 to 41 cm².Conclusion Chondroblastomas of the hands and feet share many of the radiographic characteristics seen in the long bones, but manifest in skeletally mature patients with a higher male to female ratio than in long bone chondroblastoma. Talar and calcaneal lesions were encountered only in males. Chondroblastoma of the wrist and hand appears to be exceptionally rare.Presented at the special scientific session of the International Skeletal Society held in San Francisco, California, USA, September 2003     

Evaluation of HER-2/neu status by real-time quantitative PCR in malignant cartilaginous tumors

The expression of HER-2/neu has been proposed to be a prognostic indicator in osteosarcoma. To clarify the actual frequency of HER-2/neu expression in primary malignant cartilaginous tumors, we examined 89 cases comprising 17 conventional chondrosarcomas, 33 mesenchymal chondrosarcomas, and 39 clear cell chondrosarcomas. We used real-time PCR (LightCycler) assay to quantify the HER-2/neu gene status. The crossing point of HER-2 in normal control bone was 27.77. The crossing points of HER-2 in conventional, mesenchymal, and clear cell chondrosarcomas were 28.48+/-1.79, 27.74+/-3.02, 28.57+/-1.54, respectively. In conclusion, the amplification and overexpression of the HER-2/neu oncogene is absent or at least very rare in malignant cartilaginous tumors. The level of expression of HER-2/neu was similar in all cartilaginous tumor types.     

Chikungunya virus: host pathogen interaction

Chikungunya is a re‐emerging arthropod‐borne viral disease caused by Chikungunya virus (CHIKV) belonging to the Togaviridae family of genus Alphavirus. It is a virus with a single stranded, positive sense RNA, as its genome. It is maintained in a sylvatic and urban cycle involving humans and the mosquito species Aedes aegypti and Aedes albopictus. It has garnered the attention of scientists in the past 5–6 years due to the massive outbreaks in the Indian Ocean region in 2005–2006. It has a major health impact on humans as it causes fever, rashes, arthralgia and myalgia. Polyarthralgia is the most important feature of CHIKV infection which primarily affects the small joints of the wrists and fingers along with the large joints like shoulders and knees. Currently, there are no vaccines or treatment regimens available for CHIKV infection. The molecular mechanism underlying the chronic polyarthralgia observed in patients is not well understood. In this review we have summarized the CHIKV organization, replication, epidemiology, clinical manifestations and pathogenesis with emphasis on the arthralgia. Copyright © 2011 John Wiley & Sons, Ltd.