Infection by CagA-Positive Helicobacter pylori Strains and Bone Fragility: A Prospective Cohort Study.

Helicobacter pylori (HP) infection is a common and persistent disorder acting as a major cofactor for the development of upper gastrointestinal diseases and several extraintestinal disorders including osteoporosis. However, no prospective study assessed the effects of HP on bone health and fracture risk. We performed a HP screening in a population-based cohort of 1149 adults followed prospectively for up to 11 years. The presence of HP infection was assessed by serologic testing for serum antibodies to HP and the cytotoxin associated gene-A (CagA). The prevalence of HP infection did not differ among individuals with normal bone mineral density (BMD), osteoporosis, and osteopenia. However, HP infection by CagA-positive strains was significantly increased in osteoporotic (30%) and osteopenic (26%) patients respect to subjects with normal BMD (21%). Moreover, anti-CagA antibody levels were significantly and negatively associated with lumbar and femoral BMD. Consistent with these associations, patients affected by CagA-positive strains had a more than fivefold increased risk to sustain a clinical vertebral fracture (HR 5.27; 95% CI, 2.23-12.63; p < .0001) and a double risk to sustain a nonvertebral incident fracture (HR 2.09; 95% CI, 1.27-2.46; p < .005). Reduced estrogen and ghrelin levels, together with an impaired bone turnover balance after the meal were also observed in carriers of CagA-positive HP infection. HP infection by strains expressing CagA may be considered a risk factor for osteoporosis and fractures. Further studies are required to clarify in more detail the underlying pathogenetic mechanisms of this association. © 2020 American Society for Bone and Mineral Research (ASBMR).

Preventive Role of Vitamin D Supplementation for Acute Phase Reaction after Bisphosphonate Infusion in Paget's Disease.

CONTEXT: Intravenous aminobisphosphonates (N-BPs) can induce an acute phase reaction (APR) in up to 40% to 70% of first infusions, causing discomfort and often requiring intervention with analgesics or antipyretics. OBJECTIVE: Our aim was to explore the risk factors of APR in a large sample of patients with Paget's disease of bone (PDB) and to assess the possible preventive effects of vitamin D administration. METHODS: An observational analysis was performed in 330 patients with PDB at the time of N-BP infusion. Then, an interventional study was performed in 66 patients with active, untreated PDB to evaluate if vitamin D administration (oral cholecalciferol 50 000 IU/weekly for 8 weeks before infusion) may prevent APR. RESULTS: In a retrospective study, APR occurred in 47.6% and 18.3% of naive or previously treated patients, respectively. Its prevalence progressively increased in relation to the severity of vitamin D deficiency, reaching 80.0% in patients with 25-hydroxyvitamin D (25OHD) levels below 10 ng/mL (relative risk (RR) = 3.7; 95% confidence interval (CI) 2.8-4.7, P < .0001), even in cases previously treated with N-BPs. Moreover, APR occurred more frequently in patients who experienced a previous APR (RR = 2.8; 95% CI 1.5-5.2; P < .001) or in carriers of SQSTM1 mutation (RR = 2.3; 95% CI 1.3-4.2; P = .005). In the interventional study, vitamin D supplementation prevented APR in most cases, equivalent to a RR of 0.31 (95% CI 0.14-0.67; P < .005) with respect to prevalence rates of the observational cohort. A similar trend was observed concerning the occurrence of hypocalcemia. CONCLUSIONS: The achievement of adequate 25OHD levels is recommended before N-BP infusion in order to minimize the risk of APR or hypocalcemia in PDB.

Circulating sclerostin levels and bone turnover in type 1 and type 2 diabetes.

CONTEXT: Previous observations showed a condition of low bone turnover and decreased osteoblast activity in both type 1 and 2 diabetes mellitus (DM1 and DM2). Sclerostin is a secreted Wnt antagonist produced by osteocytes that regulates osteoblast activity and thus bone turnover. Its levels increase with age and are regulated by PTH. OBJECTIVES: The aim of the present study was to evaluate circulating sclerostin levels in patients with DM1 or DM2 with normal renal function and to analyze its relationship with PTH, 25-hydroxyvitamin D, and bone turnover markers. DESIGN, AND SETTING: This was a cross-sectional study conducted at a clinical research center. PARTICIPANTS: Forty DM2 and 43 DM1 patients were studied and compared with a reference control group (n = 83). RESULTS: In the overall cohort, sclerostin levels were higher in males than in females and significantly increased with age in both genders. The positive correlation between sclerostin and age was maintained in DM1 but not in DM2 patients. Moreover, sclerostin levels were higher in DM2 than in controls or DM1 patients, and this difference persisted when adjustments were made for age and body mass index. Consistent with previous clinical and experimental observations, sclerostin was negatively associated with PTH in nondiabetic patients (r = -0.30; P < 0.01), independently of age and gender. Conversely, an opposite but nonsignificant trend between PTH and sclerostin was observed in both DM1 (r = 0.26; P = 0.09) and DM2 (r = 0.32; P = 0.07) cohorts. CONCLUSIONS: These findings suggest that sclerostin is increased in DM2. Moreover, the transcriptional suppression of sclerostin production by PTH might be impaired in both DM1 and DM2.

Influence of Helicobacter pylori infection on levels of ghrelin and obestatin in human semen.

Helicobacter pylori (HP) infection might have negative effects on the semen parameters of infertile men. We explored the possibility that this infection can influence systemic and seminal levels of ghrelin and obestatin, hormones mainly produced by the stomach. Ghrelin and obestatin exert many activities, including the regulation of reproductive biology, and are present in many organs and fluids, including human semen. In 78 men, we determined HP infection and cytotoxin-associated gene A protein (CagA) status by enzyme-linked immunosorbent assay and Western blotting, semen quality following World Health Organization guidelines, and ghrelin and obestatin levels in the blood stream (47 subjects) and semen by radioimmunoassay. Twenty-seven men (34.6%) were infected (HP+) and 11 out of 27 infected men (40.7%) were seropositive for CagA (CagA+). Sperm motility was significantly reduced in HP+/CagA+ men compared with HP+/CagA- men (P < .01). Ghrelin semen levels were decreased in HP+ men compared with uninfected individuals (P < .05), whereas they were increased in HP+/CagA+ men compared with HP+/CagA- subjects (P < .01). Ghrelin semen concentrations in HP+/CagA- men were lower than those measured in uninfected subjects (P < .001). Semen obestatin concentration was increased, in a nonsignificant manner, in HP+/CagA+ men. The obestatin levels were approximately 4 times higher than those of ghrelin in semen and approximately half the levels of ghrelin in serum specimens of all the analyzed groups. No significant differences were found in systemic levels of ghrelin and obestatin in HP+ to uninfected individuals. HP infection may influence the ghrelin seminal concentrations, probably as a response to a negative effect of infection on the semen quality.

Vitamin D as a drug.

Vitamin D has an important role in bone-metabolism (and its deficiency can cause preterm osteopenia, craniotabe and rickets), but it has also non-calcitropic functions. In fact, vitamin D deficiency is correlated to chronic kidney disease, respiratory infections, type 1 diabetes, psoriasis, Crohn disease and neonatal hypocalcemia. Because of the vitamin D deficiency is a global problem, its role as a drug is fundamental for the human health in all ages.