Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway.

OBJECTIVE: To prospectively study the relation between TSH and risk of hip and forearm fractures. DESIGN: A population-based cohort study. METHODS: In a substudy of the second survey of the Nord Trøndelag Health Study, Norway (HUNT2, 1995-97), linked with a hospital-based fracture registry, we investigated the relation between baseline TSH and risk of hip and/or forearm fractures. POPULATION: A total of 16 610 women and 8595 men aged 40 years or more, without previous self-reported thyroid disease and hip or forearm fractures. RESULTS: During 12.5 years follow-up, a total of 1870 women and 342 men experienced hip or forearm fractures. Overall, there was no relation between baseline TSH and fracture risk. However, there was weak evidence that women with TSH <0.5 and >3.5 mU/l had a slightly increased risk of hip fractures (hazard ratio (HR) 1.30, 95% CI 0.97-1.94 and HR 1.19, 95% CI 0.93-1.52) compared with the reference group with TSH of 1.5-2.4 mU/l. Supplementary analyses showed higher hip fracture risk in women with TSH >4.0 mU/l and negative thyroid peroxidase antibodies (TPOAb) compared with the reference group (HR 1.75, 95% CI 1.24-2.46). CONCLUSION: We found no statistically significant relation between baseline TSH and subsequent fracture risk, but the data suggest a weak positive association with hip fracture risk among women with both low and high TSH. The latter association was confined to women with negative TPOAb status.

Bone mineral density and vitamin D status among African American children with forearm fractures.

OBJECTIVE: To determine whether African American children with forearm fractures have decreased bone mineral density and an increased prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D level ≤ 20 ng/mL) compared with fracture-free control patients. METHODS: This case-control study in African American children, aged 5 to 9 years, included case patients with forearm fracture and control patients without fracture. Evaluation included measurement of bone mineral density and serum 25-hydroxyvitamin D level. Univariable and multivariable analyses were used to test for associations between fracture status and 2 measures of bone health (bone mineral density and 25-hydroxyvitamin D level) while controlling for other potential confounders. RESULTS: The final sample included 76 case and 74 control patients. There were no significant differences between case and control patients in age, gender, parental education level, enrollment season, outdoor play time, height, or mean dietary calcium nutrient density. Cases were more likely than control patients to be overweight (49.3% vs 31.4%, P = .03). Compared with control patients, case patients had lower whole body z scores for bone mineral density (0.62 ± 0.96 vs 0.98 ± 1.09; adjusted odds ratio 0.38 [0.20-0.72]) and were more likely to be vitamin D deficient (47.1% vs 40.8%; adjusted odds ratio 3.46 [1.09-10.94]). CONCLUSIONS: These data support an association of lower bone mineral density and vitamin D deficiency with increased odds of forearm fracture among African American children. Because suboptimal childhood bone health also negatively impacts adult bone health, interventions to increase bone mineral density and correct vitamin D deficiency are indicated in this population to provide short-term and long-term benefits.

Genetic influences on vitamin D status and forearm fracture risk in African American children.

We sought to investigate the relationship between newly identified genetic variants and vitamin D levels and fracture risk in healthy African American (black) children. This case-control study included children of both sexes, ages 5 to 9 years, with and without forearm fractures. Serum 25-hydroxy vitamin D levels, bone mineral density, body mass index, and calcium/vitamin D intake were measured in 130 individuals (n = 60 cases and n = 70 controls). The 5 variants tested were located in the GC gene (rs2282679), in the NADSYN1 gene (rs12785878 and rs3829251), and in the promoter region of the CYP2R1 gene (rs2060793 and rs104741657). Associations between single nucleotide polymorphisms (SNPs) and vitamin D levels were tested using an analysis of covariance. Associations between SNPs and fracture status were tested using logistic regression. The GC gene variant was associated with vitamin D levels (P = 0.038). None of the SNPs were associated with fracture status in young blacks. These results suggest that the variants tested, which are associated with circulating vitamin D levels in whites, are not associated with fracture status in healthy black children. Additional research is required to discover the genetics of fracture risk in blacks.

Growth hormone stimulates bone healing in a critical-sized bone defect model.

Growth hormone plays an important role in bone metabolism. Treating bone deficits is a major topic in orthopaedic surgery. Our hypothesis was that local continuous growth hormone administration stimulates bone healing in a canine critical-sized bone defect model. Bone formation in the defects was quantified using densitometric image analysis and histomorphometry. After growth hormone treatment, expression levels of insulin-like growth factors-I and II, and growth hormone receptor were determined in the bone regenerate of the original defects. Circulating plasma concentrations of insulin-like growth factors-I and II, and insulin- like growth factor binding proteins-4, and 6 were measured during treatment. Growth hormone administration resulted in healing of bone defects but without an additional effect of local infusion. Expression of insulin-like growth factor-I in the bone regenerate was lower in the growth hormone-treated dogs, whereas insulin-like growth factor-II and growth hormone receptor expression were not increased. Growth hormone increased circulating insulin-like growth factor-I and growth factor-II plasma concentrations. Continuous infusion of growth hormone stimulated bone healing in a canine critical-sized bone defect model. Local delivery of growth hormone did not additionally enhance bone healing. Increased circulating plasma concentrations of insulin-like growth factors-I and II most likely induced bone formation.

Biomarkers of joint tissue metabolism in canine osteoarthritic and arthritic joint disorders.

OBJECTIVE: To explore the levels of matrix metalloprotease-3 (MMP-3), tissue inhibitor of metalloproteases-1 (TIMP-1), 5D4 keratan sulfate, and two 3B3 chondroitin-sulfate epitopes in several canine osteoarthritic and inflammatory arthropathies. METHODS: Blood and synovial fluid were obtained from 103 dogs with rupture of the anterior cruciate ligament (ACLR), osteochondritis dissecans (OCD), fragmented coronoid process (FPC), patella luxation (PL), hip dysplasia (HD) or infectious arthritis. Dogs with non-musculosceletal disorders were used as controls. The biomarkers were measured by immunoassays. RESULTS: Median levels of synovial MMP-3, TIMP-1 and molar ratios of MMP/TIMP-1 were significantly higher in the arthritis than in the control group. The release of 5D4 keratan sulfate epitope and serum 3B3 neoepitope was reduced in arthritis patients. Increases in synovial TIMP-1 in OA were less pronounced and the molar ratio of MMP-3/TIMP-1 remained far below 1.0, demonstrating a surplus of the protease inhibitor. In osteoarthritic patients median levels of synovial 5D4 keratan sulfate were up-regulated after ACLR and PL and were inversely correlated with increasing duration of lameness. Serum TIMP-1 levels were significantly reduced in the joint disorder group when compared with the control group. CONCLUSION: Our observations present the TIMP-1 serum level as a potential marker for the detection of degenerative changes in cartilage and also indicate that in canine OA, the MMP-3 mediated matrix destruction is not of major importance. However MMP-3 seems to be a sensitive marker for the local inflammation in canine arthritis.

Local effects on the blood gas indices in diaphyseal forearm fractures.

We studied the local changes of blood gas indices of arterialised capillary blood taken simultaneously from the fractured and the uninjured arm of 30 patients with diaphyseal fractures of the forearm. Blood gases were measured with a Stat Profile 5 analyser (Nova Biomedical). The results indicate a slight but statistically significant decrease of the acid-base indices without any changes in the oxygen indices. These slight changes do not affect considerably the diagnosis of the profile.