Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies.

Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of–the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects.

Expert opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk.     

Parecoxib has non-significant long-term effects on bone healing in rats when administered for a short period after fracture

Introduction  Selective and non-selective cyclo-oxygenase (COX) inhibitors impair bone healing by inhibiting prostaglandin synthesis. The purpose of this study was to evaluate the long-term effect of parecoxib, a selective COX-2 inhibitor, on bone healing in rats, when it is applied in a pattern similar to clinical treatment patterns, that is, in a high dose and for a short period after bone fracture. Method  Closed non-displaced mid-diaphyseal fractures in the middle of the left femoral shaft were generated in each animal. In the study group, parecoxib sodium (1.06 mg/kg) was administered intra-peritoneally every day for 7 days. In the control group, normal saline was administered intra-peritoneally every day for 7 days. In both groups fracture healing (bone union and callus formation) was evaluated with X-rays 28 and 42 days after surgery. Results  Bone healing was lower in the study group (60 vs. 80% in the control group 28 days after fracture and 80 vs. 90% 42 days after fracture) but this difference was not statistically significant (P > 0.05). Conclusion  Parecoxib does not have a significant long-term effect on bone healing in rats, when it is administered in a high dose and for a short period after bone fracture. Declaration  The experiments comply with the current laws of the EU, and the protocol was approved by the Local Ethics Committee on Animal Research.     

Smoking cessation in clinical practice: predictors of six-month continuous abstinence in a sample of Greek smokers.

AIM: To identify the predictors of six-month continuous abstinence among Greek smokers treated in a Smoking Cessation Clinic, emphasising the role of sleep disturbance on the outcome. METHODS: A nested case-control design was used. Patients who attended the Smoking Cessation Clinic between November 2004 and October 2005, and who completed six months of follow-up, constituted the final study population (N=285). The patients were separated into two groups - those who managed to quit smoking and those who didn't. The cessation method included pharmacotherapy, one-to- one behavioral counselling, and follow-up by telephone communication. RESULTS: Among various baseline characteristics examined, multivariate regression analysis indicated that the time to first cigarette after awakening, and use of bupropion, independently predicted abstinence, while awakening during the night was negatively associated with abstinence. CONCLUSION: These multivariate factors, which can positively or negatively affect the outcome, should be taken into account so that smoking cessation treatment can be individualised.     

Long‐term outcome of hypertensive patients with heart failure with mid‐range ejection fraction: The significance of blood pressure control

Heart failure (HF) with mid‐range ejection fraction (HFmrEF) is a newly suggested entity in HF. Since it has been inadequately addressed, there is an urgent need to determine the profile of HFmrEF patients and the optimal approach to their management. The present study aimed to assess the long‐term clinical outcomes of hypertensive patients with HFmrEF and the impact of blood pressure (BP) on their mortality and cardiovascular outcome. We performed a retrospective observational study that included 121 hypertensive patients with HFmrEF and 149 hypertensives with heart failure and preserved ejection fraction (HFpEF). The median follow‐up was 84 months (22‐122). Our analysis did not reveal any statistically significant difference between the two groups in total mortality (P = 0.34) or cardiovascular mortality (P = 0.54). The total mean survival time was 102.9 months (100.5‐110.1), while the mean survival time was 105.3 months (80.4‐90.2) in HFpEF and 97.6 months (92.7‐102.6) in HFmrEF. An office systolic BP > 139 mm Hg and diastolic BP > 89 mm Hg were significantly associated with both all‐cause mortality (P = 0.02 and P = 0.013, respectively) and cardiovascular mortality (P = 0.02 for both). In HFpEF patients, no significant association was found between outcome and office BP. HFpEF and HFmrEF have similar long‐term outcomes. Suboptimal BP levels are a significant risk factor for an adverse outcome in HFmrEF. Our results emphasize the importance of good BP control in order to achieve better outcomes in hypertensives with impaired EF and HF symptomatology.     

Challenges in Antigenic Characterization of Circulating Influenza A(H3N2) Viruses during the 2011-2012 Influenza Season: an Ongoing Problem?

Genetic and antigenic characterization of 37 representative influenza A(H3N2) virus strains isolated in Greece during the 2011-2012 winter season was performed to evaluate matching of the viruses with the seasonal influenza vaccine strain A/Perth/16/2009. Hemagglutinin gene sequence analysis revealed that all Greek strains clustered within the Victoria/208 genetic clade. Furthermore, substitutions in the antigenic and glycosylation sites suggested potential antigenic drift. Our hemagglutination inhibition (HI) analysis showed that the Greek viruses were Perth/16-like; however, these viruses were characterized as Victoria/208-like when tested at the United Kingdom WHO Collaborating Centre (CC) with HI assays performed in the presence of oseltamivir, a finding consistent with the genetic characterization data. Variability in the HI test performance experienced by other European laboratories indicated that antigenic analysis of the A(H3N2) virus has limitations and, until its standardization, national influenza reference laboratories should include genetic characterization results for selection of representative viruses for detailed antigenic analysis by the WHO CCs.     

Neurophysiologic Evaluation of Long-Term Desferrioxamine Therapy in Beta-Thalassemia Patients

Forty patients with beta-thalassemia major (BTM), between 11 and 19 years of age and maintained on long-term desferrioxamine (DFO) treatment, were examined by evoked potential and nerve conduction velocity studies to investigate a possible involvement of the auditory, visual, somatosensory, or peripheral nervous pathways. Pathologic findings in brainstem auditory-, visual-, and somatosensory-evoked potentials, and nerve conduction velocity studies were demonstrated in 25%, 15%, 7.5%, and 25% of the patients, respectively, whereas 15% demonstrated involvement of multiple neural pathways. Subclinical involvement of the auditory pathway was statistically associated with higher mean daily DFO dose and longer duration of DFO therapy, whereas abnormalities regarding the somatosensory pathways were related to older age, longer mean duration of DFO therapy, and lower serum copper levels. Involvement of the peripheral nervous system was related to lower serum copper levels. Multiple involvement of neural pathways was related to longer mean duration of DFO therapy. We conclude that risk factors related to long-term DFO treatment are only partly responsible for the subclinical involvement of neural pathways demonstrated in beta-thalassemia major patients.     

Downgrading BIRADS 3 to BIRADS 2 category using a computer-aided microcalcification analysis and risk assessment system for early breast cancer

This paper explores the potential of a computer-aided diagnosis system to discriminate the real benign microcalcifications among a specific subset of 109 patients with BIRADS 3 mammograms who had undergone biopsy, thus making it possible to downgrade them to BIRADS 2 category. The system detected and quantified critical features of microcalcifications and classified them on a risk percentage scale for malignancy. The system successfully detected all cancers. Nevertheless, it suggested biopsy for 11/15 atypical lesions. Finally, the system characterized as definitely benign (BIRADS 2) 29/88 benign lesions, previously assigned to BIRADS 3, and thus achieved a reduction of 33% in unnecessary biopsies.     

The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction

Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD.

This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema.

Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV₁% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV₁% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients.