Part Ⅰ:Vertebral Fractures In Chinese Women Aged50Years And Older:Prevalence And Potential Risk Factors Part Ⅱ:a Novel Homozygous Mutation In The HPGD Gene Causes Primary Hypertrophic Osteoarthropathy

Objective Vertebral fracture is one of the most commonly seen symptoms of osteoporosis, and causes considerable mortality, morbidity, and economic burden. A great number of vertebral fractures are asymptomatic and go undetected, along with the lack of a standardized fracture assessment, causing the epidemiology less known compared with hip fracture. We investigated the prevalence of vertebral fractures in women over the age of50in Beijing, and analyzed the association between age, height, weight, history of non-vertebral fractures, jobs involving heavy physical labor, smoking, bone mineral density, serum biochemical parameters, and bone turnover markers and vertebral fractures.Methods A community-based population of1834women over the age of50was randomly selected in Beijing. General information including past medical history, lifestyle and exercise habits were collected through questionnaires. Serum biochemical parameters for liver and kidney function were tested. Bone turnover markers were tested by electrochemiluminescence immunoassay. Bone mineral density was detected by dual energy X-ray absorptiometry. X-ray of thoracic and lumbar spine was taken, and vertebral fractures were diagnosed using Genant’s semiquantitative technique. The age-specific prevalences were computed, and binary logistic regression was used to analyze the association between bone mineral density, potential risk factors and vertebral fracture.Results1. The age of the1834people included in this study ranged from50to89years old.46women had a history of vertebral fractures （2.5%）, and376had a history of non-vertevral fractures （20.6%）. X-ray identified112women （6.1%） had vertebral fractures.2. The prevalence of vertebral fractures increased with age, from1.2%（95%CI,0.4-2.0%） at ages50-59to20.3%（95%CI,11.4-29.2%） for women aged80years and older. A total of154vertebral fractures were identified. Multiple vertebral fractures were seen in30（26.8%） women. The vertebrae of T12and L1together accounted for54.5%of the total fractures.3. Age, BMD, and P1NP were associated with vertebral fractures. Each standard deviation decrease in bone mineral density for L2-4increased the risk about1.4-fold （95%CI,1.07-1.75）; each standard deviation decrease in bone mineral density for femoral neck increased the risk about1.3-fold （95%CI,1.02-1.58）; each standard deviation decrease in bone mineral density for total hip increased the risk about1.7-fold （95%CI,1.23-2.30）; and each standard deviation increase in P1NP increased the risk about1.2-fold （95%CI,1.02-1.51）. Long-duration daily housework was probably a protective factor for vertebral fractures. We did not found association between height, weight, menopause, nonspine fracture history, smoking, jobs involving heavy physical labor, serum biochemical parameters for liver and kidney function and other potential risk factors with vertebral fractures.Conclusion The age-specific prevalence of vertebral fractures for women over the age of50in Beijing increased with age steeply. Reduced bone mineral density was associated with increased risk for vertebral fractures, and increased bone turnover markers such as P1NP was associated with increased risk of vertebral fractures. Objective Primary hypertrophic osteoarthropathy （PHO） is a hereditary disorder featured by digital clubbing, pachyderma, hyperhidrosis, and periostosis. Mutations in HPGD gene located on chromosome4q34.1have been identified in PHO patients. The HPGD gene encodes15-hydroxyprostaglandin dehydrogenase, and mutations cause an elevation of circulating PGE2, thus the consequent manifestations in primary hypertrophic osteoarthropathy. Different mutations have been reported in families of European origin and west Asia. We investigated the mutation in HPGD gene in three Chinese families.Methods Three previously unreported Chinese families with one of more individuals affected with typical primary hypertrophic osteoarthropathy were characterized clinically. Genomic DNA was extracted from whole blood sample, and genetic analysis was performed by direct sequencing of PCR products of HPGD.Results1. All three probands were young males in their second decades. The general clinical manifestations include digital clubbing, arthropathy, hyperhidrosis, and hyperkeratosis. Acro-osteolysis, periosteal reaction, along with cortical thickening were found in radiography.2. HPGD sequence analysis identified a novel homozygous mutation, c.310₃11delCT （p.Leu104AlafsX3）, in affected individuals in all the three families. This mutation locates in exon3, which alters the open reading frame from residue104, truncating the15-PGDH protein and causing the deletion of active site and NAD binding site, thus results in loss of enzymatic function.Conclusion A novel homozygous HPGD mutation, c.310₃11delCT （p.Leu104AlafsX3）, was identified. This mutation is an frame-shift mutation, and causes the loss of NAD binding site. This mutation appears to be unique to Chinese population, and may follow autosomal recessive inheritance.