Smoking habits and osteoporosis in community-dwelling men subjected to dual-X-ray absorptiometry: a cross-sectional study.

BACKGROUND: Active and Environmental Tobacco Smoke (ETS) are a global cause of death. Osteoporosis (Op) is the most common metabolic bone disorder worldwide, impacting on mortality and disability, with high health and welfare costs. Active smoking is a known risk factor for Op, but there is few information regarding Op and ETS in men. PURPOSE: The study aim is to evaluate the association between smoking habits and Op in community-dwelling men that have been subjected to Dual-X-ray Absorptiometry and completed a questionnaire about their own and cohabiter's smoking habits. METHODS: We performed a cross-sectional study based on administrative data. This study is part of the SIMON protocol. The binary logistic regression analysis was used to estimate the role of ETS on the risk of Op, adjusting for age, body mass index (BMI), type 2 diabetes mellitus (T2DM) and eGFR. RESULTS: Four hundred sixteen men were selected and, based on questionnaire replies, 167 were classified as current smokers (CS), 93 as passive smokers (PS) and 156 as never smokers (NS). NS showed a lower prevalence of past fragility fracture, radiological features of osteoporosis and hypovitaminosis D compared to PS and CS (p < 0.05). NS showed a lower prevalence of Op compared to PS and CS, also after correction for age, BMI, T2DM and eGFR (p < 0.05). CONCLUSION: The study results demonstrate that PS and CS have a higher risk of Op, fragility fractures and vitamin D deficiency compared to NS.

Role of active and environmental tobacco smoke on susceptibility to osteoporosis in women undergoing dual-X-ray absorptiometry.

PURPOSE: Current smoking is a risk factor for osteoporosis (Op), but few data are available regarding the passive smoke impact on Op susceptibility. This cross-sectional study aimed to evaluate the association between the smoking habits and Op in community-dwelling women undergoing dual-energy X-ray absorptiometry (DXA). METHODS: On 01/06/2018, general practitioners from "COMEGEN" Medical Cooperative, Naples, Italy, selected the medical records from the last 10 years of women who had a measurement of bone mineral density performed and simultaneously completed a questionnaire about their smoking behaviour and their cohabiters'. The binary logistic regression analysis was used to estimate the role of passive smoke on the risk of Op, adjusting for age and body mass index (BMI). RESULTS: Among 10,616 subjects, 3942 were currently smokers [CS; mean age 69.4 ± 10.4 years; BMI 27.0 ± 4.9 kg/m2], 873 were passive smokers (PS; mean age 67.8 ± 11.6 years; BMI 27.0 ± 4.9 kg/m2) and 5781 were never smokers (NS; mean age 67.8 ± 11.6 years; body mass index (BMI) 27.0 ± 4.9 kg/m2). Of all, 8562 women (mean age 70.3 ± 10.2 yrs; BMI 27.0 ± 4.9 kg/m2) received the Op diagnosis. PS showed an increased Op risk compared to NS [odds ratio (OR) 1.38 (1.14-1.67)] and comparable to CS [OR 1.02 (0.84-1.24)]. CONCLUSION: The study results demonstrate an association between passive smoke and Op in community-dwelling women already presenting with susceptibility to Op according to Italian essential assistance levels, suggesting that passive and active smoke are equivalent Op risk factors in women.

Efficacy and safety of abaloparatide for the treatment of post-menopausal osteoporosis.

INTRODUCTION: Osteoporosis is a skeletal disorder characterized by loss of bone mass and strength affecting up to 30-50% of postmenopausal women worldwide. Current therapeutic options include antiresorptives such as aminobisphosphonates or denosumab and osteoanabolic compounds such as teriparatide. Areas covered: In this review, the authors summarize the clinical development, safety and efficacy profile of abaloparatide, a new osteoanabolic agent recently marketed in the US for the treatment of postmenopausal osteoporosis in women who are at high risk for fracture or who fail antiresorptive therapy. Expert opinion: Abaloparatide is a 1-34 PTH related peptide-like molecule that has been modified in order to potentiate the osteoanabolic effect. In its pivotal phase 3 trial in postmenopausal women with osteoporosis, subcutaneous abaloparatide 80 mcg/day reduced the risk of vertebral, nonvertebral, major osteoporotic, and clinical fractures compared with placebo and reduced the risk of major osteoporotic fractures compared with teriparatide. These results, together with a reduced prevalence of hypercalcemia and a lower cost of the marketed compound, point toward improved cost effectiveness with abaloparatide versus teriparatide. However, some concerns have been raised due to a somewhat higher occurrence of adverse effects (particularly with palpitations and increased heart rate) or the resultant discontinuation due to these adverse effects when compared to teriparatide.

The association of body composition and sex hormones with quantitative ultrasound parameters at the calcaneus and phalanxes in elderly women.

We investigated the associations of body composition and sex hormones with quantitative ultrasound (QUS) parameters carried out at different skeletal sites. In 897 postmenopausal women (64.1 ± 6.6 years) we measured QUS at the calcaneus (stiffness) by Achilles-GE and at phalanxes (amplitude-dependent speed of sound [AD-SOS], bone transmission time [BTT], and ultrasound bone profile index [UBPI]) by Bone Profiler-IGEA. In all subjects we measured fat mass (FM), lean mass (LM), android fat, and gynoid fat by DXA. In all subjects we also assessed serum testosterone (T), estradiol (E(2)), sex-hormone binding globulin, free estrogen index (FEI), free androgen index, 25-hydroxyvitamin D (25OHD), bone alkaline phosphatase (B-ALP), and type I collagen ß carboxy telopeptide. Both E(2) and FEI showed weak but significant correlations with stiffness and QUS parameters at phalanxes. No significant relationships were found between T and QUS. BMI and LM were positively correlated with stiffness (r = 0.14 and r = 0.17, respectively), whereas BMI and FM showed negative correlations with AD-SOS, BTT, and UBPI. 25OHD showed positive relationships with stiffness and QUS at phalanxes. In multivariate models LM and age were associated with stiffness whereas E(2) and age were significant predictors of BTT. AD-SOS was negatively associated with FM, B-ALP, and age but positively with E(2) and 25OHD. In postmenopausal women QUS parameters at the calcaneus and at phalanxes are significantly, but diversely, associated with body composition, sex hormones, 25OHD, and bone turnover markers.

Vitamin D deficiency and primary hyperparathyroidism.

Vitamin D via its receptor has essential actions on parathyroid cells, inhibiting PTH secretion, and parathyroid cell proliferation. While the effects of vitamin D depletion in the pathogenesis of secondary hyperparathyroidism in elderly individuals or in the occurrence of parathyroid hyperplasia in patients with renal insufficiency are well established, the association between hypovitaminosis D and primary hyperparathyroidism (P-HPT) has only recently become appreciated. In different cohorts of patients with P-HPT, vitamin D deficiency has been recently associated with higher PTH levels, larger adenomas, and a more severe phenotype (including osteitis fibrosa cystica) as well as negative post-operative outcomes following parathyroidectomy. Despite current guidelines recommend measurement of serum 25OHD (25-hydroxy-cholecalciferol) in P-HPT and their repletion if the levels are <20 ng/ml, future well-designed trials of vitamin D supplementation in P-HPT patients with coexisting vitamin D deficiency are needed to evaluate the risk/benefit profile of this treatment.

Bone metabolism in men: role of aromatase activity.

Sex steroid hormones play an important role in the maintenance of bone mass in males and in females. Even though androgens are the major sex steroids in men, direct and indirect evidence emerged suggesting that estrogens may also play a major role in male skeletal health. Since the testes account for only 15% of circulating estrogens in males, the remaining 85% comes from peripheral aromatization of androgen precursors in different tissues, including bone. Human models of aromatase deficiency clearly demonstrated the critical importance of the conversion of androgens into estrogens in regulating male skeletal homeostasis. Aromatase- deficient men showed tall stature due to continued longitudinal growth, unfused epiphyses, high bone turnover, and osteopenia. Interventional studies in adult men using aromatase inhibition confirmed that estrogens are important in controlling bone remodeling. Importantly either inherited (i.e. due to common polymorphisms at the human aromatase CYP19 gene) or acquired (i.e. by diseases or different compounds) variation in aromatase ability to convert androgen precursors into estrogen may also be relevant for skeletal homeostasis.

Serum OPG and RANKL levels before and after intravenous bisphosphonate treatment in Paget's disease of bone.

Paget's disease of bone (PDB) is a focal disorder of bone remodeling characterized by increased osteoclast-mediated bone resorption. Even though increasing evidence indicates enhanced nuclear factor-kB (NF-kB) signaling as a common mechanism involved in PDB and other related disorders, few studies investigated circulating osteoprotegerin (OPG) and receptor of activator of NF-kB-ligand (RANKL) levels in PDB patients. In this study we explored the relationships between OPG or RANKL levels and bone turnover markers in a group of patients with PDB, before and after intravenous bisphosphonate treatment (pamidronate 60 mg). Both OPG and RANKL were markedly elevated in PDB patients with respect to control groups (healthy or osteoporotic postmenopausal women and elderly men) and were positively associated with bone turnover markers. Higher levels of these cytokines were observed in polyostotic than monostotic PDB cases. The ratio between RANKL and OPG was more than 3-fold higher in PDB patients than in controls. Interestingly, in the group of patients treated with pamidronate, we found an increase in OPG levels that become statistically significant after 3 and 6 months from treatment. A trend toward a decrease in RANKL levels after treatment was also observed. The RANKL/OPG ratio was significantly reduced after 3 and 6 months of therapy. In contrast, in patients classified as non-responders, OPG and RANKL levels after pamidronate infusion did not significantly differ with respect to pre-treatment values. Thus, the positive effect of amino bisphosphonates in the treatment of PDB may be due to either direct or indirect suppression of RANKL-induced bone resorption through decreased RANKL and increased OPG production.

Prevalence of Helicobacter pylori infection in male patients with osteoporosis and controls.

Cytokines that regulate bone turnover (tumor necrosis factor-alpha, interleukin-6, etc.) may influence the pathogenesis of skeleton disorders, such as osteoporosis. Since Helicobacter pylori infection increases the systemic levels of inflammatory cytokines, we investigated the possibility that this infection increases the risk of developing osteoporosis and affects the bone metabolism in a group of male patients with osteoporosis. We examined 80 osteoporotic male patients and 160 controls for serum antibodies to H. pylori and the CagA protein and determined, in patients alone, the most important biochemical and instrumental parameters of the disease. Fifty-one patients (63.7%) and 107 controls (66.8%) were seropositive for H. pylori infection (nonsignificant); 30 infected patients (58.8%) and 43 infected controls (40.1%) were positive for anti-CagA antibodies (P = 0.028; OR = 2.13). Levels of estradiol in infected CagA-positive patients were significantly lower than in infected CagA-negative patients (28.5 [SD = 10.18] vs. 39.5 [SD = 14.50] pg/ml; P = 0.002) and uninfected patients (35.2 [SD = 12.7] pg/ml; P = 0.028). Levels of urinary cross-laps(a marker of bone resorption) were increased in patients infected by CagA-positive strains compared to patients infected by CagA-negative strains (282.9 [SD = 103.8] vs. 210.5 [SD = 150.1]microg/mmol; P = 0.048) and uninfected patients (204.3 [SD = 130.1] microg/mmol; P = 0.016). Differences among uninfected and infected patients, independent of CagA status, were observed for other markers of bone turnover, but they did not reach statistical significance. Infection by CagA-positive H. pylori strains is more prevalent in men with osteoporosis, who show reduced systemic levels of estrogens and increased bone turnover. H. pylori infection by strains expressing CagA may therefore be considered a risk factor for osteoporisis in men.

Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review.

Osteoporosis (OMIM166710) is a common skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue with increased susceptibility to fracture. Osteoporosis has a complex etiology and is considered a multifactorial polygenic disease in which genetic determinants are modulated by hormonal, environmental, and nutritional factors. Estrogens are known to play an important role in regulating bone homeostasis and preventing postmenopausal bone loss. They act through binding to two different estrogen receptors (ERs), ER alpha (OMIM133430) and ER beta (OMIM601663), which are members of the nuclear receptor superfamily of ligand-activated transcription factors. Different polymorphisms have been described in both the ER alpha and ER beta genes. Although a large number of association studies have been performed, the individual contribution of these polymorphisms to the pathogenesis of osteoporosis remains to be universally confirmed. Moreover, an important aim in future work will be to define their functional molecular consequences and their interaction with the environment in the causation of the osteoporotic phenotype. A further promising application of these polymorphisms comes from their pharmacogenomic implications, with the possibility of providing better guidance for therapeutic regimens, such as estrogen replacement therapy and selective ER modulators. At the moment, no recommendations for population-based screening can be made.

Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status.

Quantitative ultrasound (QUS), although widely used in adults has, so far, been scarcely employed in newborn infants and children. This study aimed to evaluate the feasibility of the use of QUS in newborn children and the factors influencing QUS parameters. In 140 consecutive healthy full-term newborn babies (76 male and 64 female; gestational age: 39.5 +/- 1.5 weeks) QUS parameters were assessed within 3 days of the child's birth at the distal diaphysis of the humerus by use of Bone Profiler, after an appropriate modification of caliper and software. In all subjects we evaluated the amplitude-dependent speed of sound (AD-SoS) (meters per second), the characterizing graphic trace parameters [signal dynamic (SDy), fast wave amplitude (FWA) and bone transmission time (BTT)], SoS (meters per second), that is, the speed of sound calculated on the first peak, and hBTT, that is, the interval time between the first peak of the ultrasound and when this reaches the speed of 1,570 m/s, which is the velocity of ultrasound in the soft tissue. This latter parameter allows one to measure bone tissue independently of soft tissue. QUS measurements were also performed at the phalanges on all mothers (age range 24-38 years), who also completed a self-report questionnaire on their obstetric history, smoking and dietary habits and family history of osteoporosis. In 73 mothers and their children QUS was repeated after 12 months. All QUS parameters were slightly higher in male than in female newborn infants but the difference was not significant. BTT and hBTT of neonates showed a significant relationship with birth weight (r = 0.20; P < 0.05 and r = 0.37; P < 0.01, respectively) and with cranial circumference (r = 0.22; P < 0.05 and r = 0.36; P < 0.01, respectively). In newborn infants none of the QUS parameters was significantly influenced by maternal QUS or by maternal smoking and calcium intake. In a model of multiple regression analysis the cranial circumference was the only parameter entered into the model, explaining approximately 15% of hBTT value. At month 12 AD-SoS and SoS were slightly lower than at birth (-11% and -0.1%, respectively), whereas both BTT and hBTT showed a significant (P < 0001) increase. The present study demonstrated the feasibility of the use of QUS, as assessed by a new measurement approach at the humerus, in the evaluation of skeletal status in neonates. BTT and, above all, hBTT, appears to be the best parameter for both evaluation of skeletal status at birth and monitoring of bone growth in the first year of life.