Glucocorticoid-induced osteoporosis (GIO) is the most common form of secondary osteoporosis. Fractures, which are often asymptomatic, may occur in as many as 30-50% of patients receiving chronic ...glucocorticoid therapy. Vertebral fractures occur early after exposure to glucocorticoids, at a time when bone mineral density (BMD) declines rapidly. Fractures tend to occur at higher BMD levels than in women with postmenopausal osteoporosis. In human subjects, the early rapid decline in BMD is followed by a slower progressive decline in BMD. Glucocorticoids have direct and indirect effects on the skeleton. The primary effects are on osteoblasts and osteocytes. Glucocorticoids impair the replication, differentiation and function of osteoblasts and induce the apoptosis of mature osteoblasts and osteocytes. These effects lead to a suppression of bone formation, a central feature in the pathogenesis of GIO. Glucocorticoids also favor osteoclastogenesis and as a consequence increase bone resorption. Bisphosphonates are effective in the prevention and treatment of GIO. Anabolic therapeutic strategies are under investigation.
Purpose
Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal ...fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future.
Methods
A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus.
Results
Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders.
Conclusions
Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures.
Bone fragility in men who are treated with androgen deprivation therapy (ADT) has a complex pathophysiology that differs from that of primary and post-menopausal osteoporosis. Fracture risk ...assessment based on bone mineral density (BMD) and Fracture Risk Assessment Tool (FRAX) score might not be effective in this patient setting, since high frequency of fragility fractures has been reported even in subjects with low FRAX risk and normal BMD. In this paper we want to emphasize the importance in the individual assessment of bone fragility and prediction of fractures by measuring parameters of bone quality, assessing morphometric vertebral fractures and evaluating body composition that in subjects under hormone-deprivation therapies can play a crucial role. Noteworthy, a single mini-invasive diagnostic tool, i.e., the dual energy x-ray absorptiometry (DXA) scan, offers the opportunity to evaluate reliably parameters of bone quality (e.g., trabecular bone score) and body composition, besides measurement of BMD and assessment of vertebral fractures by a morphometric approach. This article highlights the values and cost-effectiveness of this mini-invasive tool in the context of multidisciplinary approach to subjects with prostate cancer under ADTs.
The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce ...the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI.
Context:
Cross-sectional studies showed an elevated prevalence of vertebral fractures in acromegaly. However, no data are available on incident vertebral fractures in this clinical setting.
...Objective:
The objective of the study was to investigate the incidence and risk factors of vertebral fractures in patients with acromegaly.
Design:
This was a 3-year prospective study.
Setting:
The study was conducted at referral centers.
Subjects:
Eighty-eight patients with acromegaly (33 females, 55 males; mean age 50 years, range 21–85 years) and 106 control subjects, matched for sex and age (43 females and 63 males, mean age 55 years, range 33–79 years), attending outpatient bone clinics participated in the study.
Main Measures:
Patients and control subjects were evaluated for the incidence of vertebral fractures using a quantitative morphometric approach on spine x-ray, which was performed at baseline and after 3 years of follow-up. At the same time points, patients with acromegaly were also evaluated for bone mineral density with dual-energy X-ray absorptiometry at lumbar spine and femoral neck.
Results:
After a 3-year follow-up, 37 patients with acromegaly (42.0%) and 4 control subjects (3.8%) experienced incident vertebral fractures (P < .001). The incidence of vertebral fractures was significantly higher in patients with active disease as compared with those who had controlled/cured acromegaly at the study entry (62.5% vs 25.0%; P < .001). The risk of incident vertebral fractures was significantly associated with hypogonadism, a change in the femoral neck bone mineral density, and prevalent vertebral fractures at the study entry only in patients with controlled/cured acromegaly, whereas in patients with active disease, the fracture risk was not influenced by the above-mentioned clinical factors, but it was significantly associated with the duration of active acromegaly.
Conclusions:
This prospective study demonstrates a high rate of incident vertebral fractures both in patients with active and controlled acromegaly.
In this paper response surface methodology (RSM) was used to study the transesterification reaction of rapeseed oil for biodiesel production. The three main factors that drive the conversion of ...triglycerides into fatty acid methyl esters (FAME) were studied according to a full factorial design at two levels. These factors were catalyst concentration (KOH), temperature and reaction time. The range investigated for each factor was selected taking into account the process of Fox Petroli S.p.A. Analysis of variance (ANOVA) was used to determine the significance of the factors and their interactions which primarily affect the first of the two transesterification stages. This analysis evidenced the best operating conditions of the first transesterification reaction performed at Fox’s plant: KOH concentration 0.6% w/w, temperature 50
°C and reaction time 90
min with a CH
3OH to KOH ratio equal to 60. Three empirical models were derived to correlate the experimental results, suitable to predict the behavior of triglyceride, diglyceride and monoglyceride concentration. These models showed a good agreement with the experimental results, demonstrating that this methodology may be useful for industrial process optimization.
To summarize promising areas of investigation in osteoporosis and to stimulate further research in this area, as discussed in a recent international conference. Over the recent years, there has been ...an improvement in the knowledge of molecular pathways involved in bone formation and resorption with the development of new drugs to treat osteoporosis. Intact parathyroid hormone, teriparatide, and anti-sclerostin monoclonal antibody are anabolic drugs, whereas denosumab and odanacatib are anti-resorptive drugs with more reversible effects as compared to bisphosphonates. Anabolic and anti-resorptive agents have different effects on bone, and research in this area includes the efficacy of combination and sequential therapies with them. New insights in the molecular pathways of bone remodeling have clarified the mechanisms responsible for skeletal fragility in several forms of secondary osteoporosis, such as that occurring in type 2 diabetes, following drug exposure and systemic inflammatory diseases. Future research is needed to address the efficacy of anti-osteoporotic drugs in these more recently recognized conditions of skeletal fragility. Osteoporosis continues to be an important field of biomedical research.
The central role of vitamin D in bone health is well recognized. However, controversies regarding its clinical
application remain. We therefore aimed to review the definition of hypovitaminosis D, ...the skeletal and extra-skeletal effects of vitamin D and the available therapeutic modalities.
Narrative and systematic literature review.
An international working group that reviewed the current evidence linking bone and extra-skeletal health
and vitamin D therapy to identify knowledge gaps for future research.
Findings from observational studies and randomized controlled trials (RCTs) in vitamin D deficiency are
discordant, with findings of RCTs being largely negative. This may be due to reverse causality with the illness itself contributing to low vitamin D levels. The results of many RCTs have also been inconsistent. However, overall evidence from RCTs shows vitamin D reduces fractures (when administered with calcium) in the institutionalized elderly. Although controversial, vitamin D reduces acute respiratory tract infections (if not given as bolus monthly or annual doses) and may reduce falls in those with the lowest serum 25-hydroxyvitamin D (25OHD) levels. However, despite large ongoing RCTs with 21 000–26 000 participants not recruiting based on baseline 25OHD levels, they will contain a large subset of participants with vitamin D deficiency and are adequately powered to meet their primary end-points.
The effects of long-term vitamin D supplementation on non-skeletal outcomes, such as type 2 diabetes
mellitus (T2DM), cancer and cardiovascular disease (CVD) and the optimal dose and serum 25OHD level that balances extra-skeletal benefits (T2DM) vs risks (e.g. CVD), may soon be determined by data from large RCTs.
Romosozumab, a fully humanized anti-sclerostin-antibody, is a bone-builder stimulating osteoblasts and inhibiting osteoclast by activation of the canonical Wnt-beta catenin signaling. This unique ...mechanism of action has the potential to address unmet needs in osteoporosis management.
The multifaceted practical clinical issues related to romosozumab are discussed, especially focusing on the rationale of employing a sclerostin inhibitor to target bone fragility as first line or second line treatment in post-menopausal osteoporosis and in males at increased risk of fractures.
Four randomized clinical trials with several post-hoc analyses and more than ten observational studies have consistently demonstrated that romosozumab is effective in rapidly increasing bone mineral density (BMD) and decreasing risk of vertebral, non-vertebral and hip fractures in post-menopausal women at very-high risk of fractures. In male osteoporosis, only data on BMD are available. Noteworthy, romosozumab was shown to be more effective and rapid than teriparatide in improving BMD, bone structure and strength at the hip, especially in women already treated with anti-resorptive drugs. Interestingly, even if romosozumab displays best results in treatment-naïve patients, its favourable effects on BMD were observed even in women previously treated with teriparatide or denosumab, although to a lesser extent.
Based on the available evidence, romosozumab could be proposed as ideal drug in several clinical settings, such as non-fractured post-menopausal women at very-high risk of fractures, patients with recent hip fracture, patients non responder to bisphosphonates and short-term denosumab therapy.
Activated carbon adsorbate loading at equilibrium (ω*) as a function of initial mercury concentration (c0), temperature and oxygen partial pressure. Symbols: experimental results; lines: model ...results.◊ pO2=99.3kPa, □ pO2=20.8kPa, ○ pO2=4.9kPa, + pO2=0kPa (100% N2). Display omitted
•We studied Hg0 adsorption on activated carbon in different O2/N2 streams.•The experiments led to the determination of the breakthrough curves for fixed bed.•The influence of oxygen during pre-treatment and during adsorption is studied.•Experiments showed that O2 in the gas phase increases the adsorption capacity.•Oxygen has a twofold effect, increasing active sites and modifying carbon surface.
The main purpose of this paper is the study of elemental mercury adsorption phenomena on a commercially available activated carbon in different oxygen/nitrogen streams. A laboratory-scale apparatus with a fixed bed was used to adsorb elemental mercury vapors in an oxygen/nitrogen stream (synthetic gas). Temperature was varied from 90 to 150°C. The inlet gas stream was a nitrogen/oxygen mixture with oxygen partial pressures varying from 4.9 to 99.3kPa, in this gas stream elemental mercury vapors was added spanning the mercury concentration from 0.3 to 3mg/m3. A commercial activated carbon (Darco G60 from BDH) was utilized as sorbent.
The experiments led to the determination of the breakthrough curves for the fixed bed. Saturation data allow determining the adsorption isotherms for the temperatures tested, at the different oxygen partial pressures investigated. Experiments showed that the presence of oxygen in the gas phase increases the adsorption capacity of the sorbent and the higher the oxygen concentration the higher the adsorption capacity; however an unusual trend of the adsorption capacity as a function of the temperature was observed, suggesting the occurrence of different phenomena. In order to explain this trend a set of ad hoc experiments was realized pre-treating the carbon in oxygen/nitrogen gas phase and performing the adsorption of mercury in a nitrogen gas phase. These experiments allow the definition of a new model that accounts for the phenomena occurring during mercury adsorption in gas phase containing oxygen. Eventually, the model results well fit the experimental findings.
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