Anti-osteoporosis Drugs Research Articles

“EFFECT OF CROSSLINKING AGENT ON DEVELOPMENT OF GASTRORETENTIVE MUCOADHESIVE MICROSPHERES OF RISEDRONATE SODIUM”

Objective: The present investigation was undertaken to develop and evaluate a gastroretentive mucoadhesive microspheres of anti-osteoporosis drug risedronate sodium to enhance the residence time and drug release by studying the effect of the crosslinking agent to obtain the best formulation with reduced particle size and good in vitro mucoadhesion strength.Methods: Selected drug risedronate sodium is a potent pyridinyl bisphosphonate used for the treatment of osteoporosis, and other bone disorders. Microspheres using sodium alginate as a polymer and calcium chloride solution as a cross-linker were prepared successfully by the emulsification crosslinking method. The 23 factorial design was used to study the effects of various variables like a drug: polymer ratio, crosslinking agent concentration and crosslinking time on the particle size and in vitro mucoadhesion strength. All these formulations were evaluated for entrapment efficiency, percentage yield and cumulative drug release. F1 batch was selected as best formulation and evaluated for scanning electron microscopy, fourier transforms infrared spectroscopy, differential scanning calorimetry, stability study.Results: Design batches were evaluated for percent yield (61.29-89.33%), % entrapment efficiency (42.25±0.620-62.58±0.330), mucoadhesion strength (68.15±0.37-82.24±0.72%) and drug release at 12 h (67-84%). Among the microspheres formulation, an F1 batch of (0.5:1) drug: polymer concentration and at 4% concentration of calcium chloride as a crosslinker was considered best formulation with reduced particle size 32.85±0.774μm, % intro mucoadhesion. 82.24±0.72. In vitro mucoadhesion strength was increased with the increasing crosslinking time from 5 min to 10 min. The fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) study showed no interaction between drug and polymer. X-ray diffraction (XRD) spectrum of microspheres indicates that drug particles are dispersed at the molecular level in the polymer matrices so no indication of the crystalline nature of the drug nature. Scanning electron microscopic (SEM) study showed that microspheres were spherical in shape with a smooth surface. F1 batch shows percentage cumulative drug release 84.07%. In vitro dissolution studies indicates that percent cumulative drug release from microspheres follows zero order kinetics plot which indicates controlled-release drug-delivery for 12 h which leads to control of plasma concentration.Conclusion: The results show that the formulation that contains (0.5:1) drug: polymer ratio, calcium chloride in 4% concentration and crosslinking time 10 min is the best one and can be utilized to formulate risedronate sodium mucoadhesive microspheres to enhance gastric residence time, improved patient compliance and reduction in the frequency of drug administration.

Anti-osteoporosis drug use: too little, too much, or just right? The HUNT study, Norway.

To examine the use of anti-osteoporotic drugs (AODs) and to identify predictors for prescriptions. Data were obtained from the Nord-Trøndelag Health Study (HUNT3) performed in 2006-2008 and the Norwegian Prescription Database, including 15,075 women and 13,386 men aged 50-85years. Bone mineral density (BMD) in the femoral neck was measured in a subgroup of 4538 women and 2322 men. High fracture risk was defined as a FRAX score for major osteoporotic fracture (MOF) ≥ 20%; in the subgroup with BMD, high risk was in addition defined as FRAXMOF ≥ 20% or T-score ≤ - 2.5. Hazard ratios (HRs) for predictors of incident use of AODs within 2years after HUNT3 were estimated by Cox' proportional hazards model. Among individuals with FRAX MOF ≥ 20%, 25% of the women and 17% of the men were treated with AODs. Among those with FRAX MOF < 20%, 3% and 1% were treated, respectively. In the subgroup with BMD measurement, 24% of the women and 16% of the men at high risk of fractures were treated, compared to 3 and 1% in women and men not fulfilling the criteria. In women, high age was the strongest predictor for treatment (HR 3.84: 95% confidence interval 2.81-5.24), followed by use of glucocorticoids (GCs) (2.68:1.84-3.89). In men, predictors were use of GCs (5.28: 2.70-10.35) followed by multimorbidity (3.16:1.31-7.63). In the subgroup with BMD, T-score ≤ - 2.5 was the strongest predictor (women 3.98:2.67-5.89; men 13.31:6.17-28.74). This study suggests an undertreatment of AODs in individuals at high risk of fracture.

Understanding osteoporotic pain and its pharmacological treatment.

Osteoporosis, a disorder that affects millions of people worldwide, is characterized by decreased bone mass and microstructural alterations giving rise to an increased risk of fractures. Osteoporotic fractures can cause acute and chronic pain that mainly affects elderly patients with multiple comorbidities and commonly on different drug regimens. The aim of this paper is to summarize the pathogenesis and systemic treatment of osteoporotic pain. This narrative review summarizes the main pathogenetic aspects of osteoporotic pain and the cornerstones of its treatment. Osteoporotic fractures induce both acute and chronic nociceptive and neuropathic pain. Central sensitization seems to play a pivotal role in developing and maintaining chronicity of post-fracture pain in osteoporosis. Antiosteoporosis drugs are able to partially control pain, but additional analgesics are always necessary for pain due to bone fractures. Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors reduce acute pain but with a poor effect on the chronic neuropathic component of pain and with relevant side effects. Opioid drugs can control the whole spectrum of acute and chronic bone pain, but they differ with respect to their efficacy on neuropathic components, their tolerability and safety. Chronic pain after osteoporotic fractures requires a multifaceted approach, which includes a large spectrum of drugs (antiosteoporosis treatment, acetaminophen, NSAIDs, selective COX-2 inhibitors, weak and strong opioids) and non-pharmacological treatment. Based on a better understanding of the pathogenesis of osteoporotic and post-fracture pain, a guided stepwise approach to post-fracture osteoporotic pain will also better meet the needs of these patients.

Gender differences in anti-osteoporosis drug treatment after osteoporotic fractures.

This study examined differences between men and women in factors affecting anti-osteoporosis drug treatment after osteoporotic fracture. Using a national claims database, we analyzed patients aged 50years and older who experienced their first osteoporotic fracture between January 1, 2008, and December 31, 2012. We examined whether patients were prescribed anti-osteoporosis drugs within 6months post-fracture. Factors associated with treatment status were identified using multivariate logistic regression. Among a total of 556,410 patients aged 50 and older, only 37% were prescribed anti-osteoporosis drugs within 6months post-fracture. Female patients with fractures were more likely to receive pharmacotherapy than male patients (41.7 vs. 19.3%). Older age significantly increased the likelihood of receiving anti-osteoporosis drugs after osteoporotic fracture. For men, the adjusted odds ratio for receiving therapy was greatest in those aged 80years and older (OR 6.4), and for women, it was largest in those aged 70-79 (OR 3.33). Both men and women were more likely to be prescribed drugs after a spine fracture, with men having significantly greater odds of receiving drug therapy (men, OR 7.1, 95% CI 6.5-7.9; women 4.79, CI 4.63-4.96). Patients with rheumatic disease or other osteoporosis-inducing comorbid disease were more likely to be prescribed anti-osteoporosis drugs. Our findings indicate that a lack of anti-osteoporosis pharmacotherapy after fracture remains a problem in Korea, especially among men, highlighting the need for effective quality improvement interventions to maximize post-fracture treatment rates.

A network meta-analysis on the short-term efficacy and adverse events of different anti-osteoporosis drugs for the treatment of postmenopausal osteoporosis.

A network meta-analysis was conducted to compare the short-term efficacy and adverse events of different drugs for the treatment of postmenopausal osteoporosis (PMO), providing a more effective treatment for PMO. We initially searched through various databases like PubMed, Cochrane Library, and EMBASE from inception till October 2016. All randomized controlled trials (RCTs) of drugs for the treatment of PMO were included for direct and indirect comparison. A combination of direct and indirect evidence of different inhibitors of anti-diabetic drugs for treatment of PMO were considered for calculating the weighted mean difference (WMD) value or odd ratio (OR) value and to draw surface under the cumulative ranking (SUCRA) curves. Twenty-seven RCTs were ultimately incorporated into this network meta-analysis comprising of 48 200 patients suffering from PMO. The network meta-analysis revealed that compared with placebo, alendronate had better efficacy on improving bone mineral density (BMD) at lumbar spine, femoral neck, and total hip. Risedronate and raloxifene had relatively lower incidence of new vertebral fractures. The SUCRA analysis showed that alendronate had better efficacy on improving BMD, risedronate could significantly decrease the incidence of fresh fracture and bazedoxifene was relatively safe. The available evidence suggested that alendronate and risedronate might be the superior choices for the treatment of PMO, while bazedoxifene was a comparatively safer option for patients.

Clinical efficacy of one-stage posterior debridement, Smith-Petersen osteotomy, compressive fusion and instrumentation for treatment of thoracolumbar tuberculosis

Objective To discuss the clinical efficacy and surgical indications of one-stage posterior debridement, Smith-Petersen osteotomy(SPO), compressive fusion and instrumentation for treatment of thoracolumbar tuberculosis. Methods All of 32 patients with thoracolumbar spinal tuberculosis were retrospectively analyzed, treated by one-stage posterior debridement, SPO, compressive fusion and instrumentation from March 2010 to October 2016, including 23 males and 9 females, aged 2 to 77 years old, average (39.2±17.8) years. All patients were treated by preoperative quadruple anti-tuberculosis drugs therapy for 2-4 weeks, postoperative regular chemotherapy for 12-18 months. Preoperative and postoperative changes in clinical symptoms, nervous function, the situation of the erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP) with strict follow-up, as well as other related complications were observed. The spinal fusion rate and fusion situation, changing of the physiological curvature, as well as loosening or breaking of the internal fixation device were detected through regular imaging examination. Results The surgery duration time was 90-150 min, average (120±19.6) min, and the blood loss was 150-600 ml, average (320±88.9) ml. Postoperative follow-up time was 1 to 3 years, average 2.3 years. The symptoms of tuberculosis poisoning in all patients were obviously relieved and the nutritional status was improved gradually. The visual analogue scale(VAS) improvement rate was about 92%. The VAS score in the preoperative and the last follow-up was statistically significant. All patients' ESR and CRP returned to normal levels at the last follow-up. The Kirkaldy-Willis function score showed that the total fine rate was 93.75%. 9 patients with spinal neurological impairment were postoperative improved significantly. Except 1 patient’s Asia grade improved from the B to C, others returned to normal condition. 30 cases recovered. Pleural effusion was observed in 3 cases treated with closed thoracic drainage and antibiotics. The drainage tube was removed after 5-7 d. Incision fistula were observed in 1 patient at 1 month after discharge and recovered after debridement and drugs adjustment. Internal fixation loosening was found in 1 elderly patient after 6 months after surgery which was treated with hyperextended brace and anti-osteoporosis drugs. No tuberculosis recurrence was found. Conclusion One-stage posterior debridement, SPO, compressive fusion and instrumentation is a simple, effective and safety surgical approach, which has great application value for surgical treatment of patients with thoracolumbar spinal tuberculosis. Key words: Thoracic vertebrae; Lumbar vertebrae; Tuberculosis, spinal; Spinal fusion

Prospect of Combination and Sequential Therapies for Postmenopausal Osteoporosis.

Osteoporosis is a systemic bone disease, which is associated with the osteoporotic fracture. Along with prolonged life expectancy, the fracture risk increases dramatically with age. So far, it is usually the first choice to using antiresorptive agents. However, current clinical therapeutic treatments are not enough to inhibit the long-term bone loss and the rising risk of bone fractures. Recently, combination and sequential therapies with anti-osteoporosis drugs have become an inevitable trend. The purpose of this review is to summarize the present knowledge related to the combination and sequential therapies with anti-osteoporosis drugs. All articles published in PubMed until 2016 on the combination and sequential therapies with antiosteoporosis drugs were reviewed and the relevant literature was described in this review. As the first-line therapy for osteoporosis, the long-term safety and efficacy on bisphosphonate, teriparatide, and new anti-osteoporosis drugs are ongoing concerns. Combination or sequential therapies of boneforming agents and anti-resorptive agents, or two kinds of anti-resorptive agents, or strontium ranelate and other anti-osteoporosis agents have the advantages on BMD compared with monotherapy. So far, it is still an important public health strategy to therapy on the osteoporosis and related fracture. Alternatively, the combination and sequential therapies with anti-osteoporosis drugs are promising approaches for prevention and treatment of osteoporosis and have far-reaching significance.

RNA-Seq investigation and in vivo study the effect of strontium ranelate on ovariectomized rat via the involvement of ROCK1

Strontium ranelate (SrR) is an anti-osteoporosis drug with excellent osteogenic and angiogenic capacity. In this study, we aimed to investigate the osteogenesis and angiogenesis effects of SrR and the underlying mechanism involved. RNA-Seq was conducted to examine the effects of SrR on gene expression in ovariectomy rat bone marrow mesenchymal stem cells (OVX-rBMSCs). To validate the different expressed gene in vitro, the effects of gene interference and overexpression in osteogenic induction environment of OVX-rBMSCs and in primary osteoblasts were studied. RNA-Seq showed that ROCK1 significantly increased after SrR treatment in OVX-rBMSCs, and further validated by real-time PCR and western blotting. Overexpression of ROCK1 promoted osteogenic differentiation of OVX-rBMSCs and induced cell viability and inhibited apoptosis of primary osteoblasts, which was reversed by inhibition of ROCK1 by RNA interference or ROCK1 inhibitor (Y-27632) after SrR treatment. Furthermore, the SrR was loaded on nano-structured hydroxyapatite (nano-HAp) particulates to promote osteogenesis and angiogenesis in repairing of the femoral condyle bone defect using ovariectomy rat model. Taken together, ROCK1 is one of the targets that SrR promotes the osteogenic differentiation of OVX-rBMSCs and cell viability of primary osteoblasts, the nano-HAp particles could act as carriers for SrR to repair bone defects.

Review Venous Thromboembolism Risk with Anti-Osteoporosis Drugs

Osteoporosis is the most common skeletal diseases, predisposing the patient to an increased risk of fractures. It is an important health issue linked to increased morbidity and mortality. Prevention and treatment strategies are now well defined and are always updating. Indeed, the therapeutic decision is based on the individual risk of fracture, efficiency and degree of therapeutic tolerance. However, some side effects, although rare can be attributed to drugs used. The benefit and risks of prescription drugs can be optimized by choosing the right time and the right treatment. The purpose of this article is the study of thromboembolic risk of various drugs recommended in osteoporosis. Furthermore we discuss preventive measures, and the different approaches after the first event.

The effects of minodronate and activated vitamin D on bone mineral density and muscle mass in postmenopausal women with osteoporosis.

Introduction Osteoporosis and sarcopenia are said to be similar disorders. However, few reports have described the effects of anti-osteoporosis drugs on muscle mass in clinical practice. Methods We selected 150 postmenopausal women with osteoporosis treated by minodronate (osteoporosis medication [OM] group) and 50 postmenopausal women without osteoporosis who did not receive treatment (no osteoporosis [NO] group). The OM group was further divided into two treatment subgroups: a combination of monthly minodronate and daily activated vitamin D vs. monthly minodronate alone. We measured lumbar spine and femoral neck bone mineral density (BMD) with dual-energy X-ray absorptiometry and muscle mass of the upper limbs, lower limbs, and trunk with bioelectrical impedance analysis at baseline and after 6 months. Results The OM and NO groups contained 130 and 37 patients, respectively (mean age: 73.9 ± 8.3 and 74.1 ± 10.0 years, respectively). In the OM group, lumbar spine BMD significantly increased after 6 months, while lower limb muscle mass significantly decreased. In the NO group, lumbar spine BMD and lower limb muscle mass did not significantly change after 6 months. In the OM group, BMD of the lumbar spine significantly increased but the lower limb muscle mass significantly decreased after 6 months relative to the NO group. In the combination therapy subgroup of the OM group muscle mass decreased significantly less than in the minodronate-alone subgroup. Conclusions In postmenopausal women with osteoporosis, minodronate can increase BMD but cannot increase muscle mass. However, simultaneous use of activated vitamin D can suppress muscle mass decrease. The combination of activated vitamin D and minodronate may be useful for treating osteoporosis in postmenopausal women.

Osteon Myospalacem Baileyi attenuates osteoclast differentiation through RANKL induced NFAT pathways

Ethnopharmacological relevanceOsteon Myospalacem Baileyi, known as Sai long gu (Tibetan language, means “blind rat bone”), is the whole skeleton of Tibet plateau rodentia animal Myospalacem Baileyi. Osteon Myospalacem Baileyi had been widely used in the Tibet region as an anti-osteoporosis drug and since 1991 Osteon Myospalacem Baileyi has been listed in the Pharmacopoeia of People's Republic of China as the first-class animal new medical material. However, the mechanism of its anti-osteoporosis activities is still unclear. It is very desirable to solve this problem for further study. Materials and methodsin this study, preparative chromatography was employed to produce the active fraction ET4 from Osteon Myospalacem Baileyi crude. Flow cytometry and MTT assay were used to evaluate the toxicities of ET4. BMM cells were separated from mouse bone marrow to test the inhibition effects of ET4 on osteoclastogenesis. Western blot was used to find out the pathways, through which ET4 could act on osteoclastogenesis. Q-PCR was used to test the osteoclastogenesis marker genes. At last, immunofluorescence confocal microscopy was used to test the osteoclastogenesis master protein NFATc1 nuclei translocation. ResultsIn this study we report that ET4, at the dose of 60μg/mL, significantly inhibited the formation of osteoclasts. Notably, ET4 did not affect the BMM viability at that dose. In addition, Osteon Myospalacem Baileyi could inhibit the expression of osteoclast marker genes, including cathepsin K (CTSK), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAP, Acp5) dendrite cell-specific transmembrane protein (DC-STAMP), calcitonin receptor (CTR), osteoclast associated and immunoglobulin-like receptor (OSCAR). Mechanistically, ET4 dose- and time-dependently blocked the RANKL-induced activation of ERK and c-Fos as well as the induction of NFATc1 which is essential for OC formation. ConclusionsThese data suggest that ET4 might be a useful alternative therapy in preventing or treating osteolytic diseases.

Investigation and analysis of osteoporosis, falls, and fragility fractures in elderly people in the Beijing area: a study on the bone health status of elderly people ≥ 80years old with life self-care.

The purpose of this study is to investigate prevalence of osteoporosis, falls, and fragility fractures in this population, and analyze related factors, in order to provide a basis for standardized prevention and treatment. From August 2015 to August 2016 in Beijing City, a total of 175 elderly individuals, who were ≥ 80years old and had good self-care ability, were included into this study. The questionnaire, risk of falls, grip force, and walking speed were measured, and the Timed Up and Go test (TUG) and chair-rising test (CRT) were performed. Compared to women, men have higher rates of smoking, drinking, drinking strong tea, longer outdoor activity time, as well as larger muscle strength and pace, and lower consumption of dairy products, fall risk assessment scale (FRA) score, 25OHD, administration rates of calcium and anti-osteoporosis drugs (P < 0.05, P < 0.01). Compared with men, women had higher bone turnover markers (P1NP, β-CTx, and OC) (P < 0.05, P < 0.01) and lower levels of sex hormones (E2, T) (P < 0.01). The overall prevalence of osteoporosis was 24.6%, and this was significantly higher in women than in men (52.5 vs. 9.6%, P < 0.01). Among these subjects, 62.9% had a history of fall after 80years old, and this rate was higher in women than in men (77 vs. 55.3%, P < 0.01). The overall prevalence of fragility fractures was 25.1%, which was higher in women than in men (45.9 vs. 14.0%, P < 0.01). Risk factors included falls after age 80, high FRA score, and reduction in bone density of lumbar vertebrae 1-4, and odds ratio (OR) was 12.195, 1.339, and 0.076, respectively (P < 0.01). Anti-osteoporosis therapy was only performed on a small number of patients with fractures. The prevalences of falls, prior fracture, and low BMD were high among ≥ 80years old and under life self-care in the Beijing area. Therefore, a comprehensive approach to assessment and treatment should be promoted.

Comment on: Patients' preferences for anti-osteoporosis drug treatment: a cross-European discrete choice experiment.

Comment on: Patients' preferences for anti-osteoporosis drug treatment: a cross-European discrete choice experiment.

Comment on: Patients' preferences for anti-osteoporosis drug treatment: a cross-European discrete choice experiment: reply.

_SIR,_ We are grateful to Dr Armstrong for sharing his views and concerns about our recent paper that elicited patients’ preferences for osteoporosis drug treatment using a cross-European discrete-choice experiment (DCE). First, the correspondent questioned the use of DCE in the area of osteoporosis therapy. Although the application of DCEs within healthcare is relatively new, DCEs are nowadays increasingly used to elicit preferences for various healthcare conditions and purposes. Previous DCEs were already conducted in osteoporosis, suggesting that respondents were able to discriminate between medication attributes and that a DCE could be suitable in the area of osteoporosis. Our study confirms this finding. [...]

Effects of health education intervention in elderly patients with osteoporosis

Objective To examine changes in bone mineral density, serum bone turnover markers and serum cytokines after health education intervention in elderly patients with osteoporosis. Methods Two hundred and twenty elderly patients with osteoporosis were randomly divided into two groups.The control group(n=110)was given routine treatment, including anti-osteoporosis drugs and daily supplements of calcium and vitamin D. In addition to routine drug treatment, the observation group(n=110)also underwent health education intervention, which included instructions on lifestyle, diet, and exercise.After one year follow-up, levels of bone mineral density(BMD), propeptide of type I procollagen(PINP), β-crosslaps(β-CTX), parathyroid hormone(PTH), 25-dihydroxyvitamin D[25(OH)VD], interleukin-2(IL-2), and insulin-like growth factor-1 receptor(IGF-1R)were analyzed. Results After one year follow-up, all indicators, except the β-CTX level, were significantly improved in the observation group compared with those in the control group(all P<0.05). Mean while, compared with pre-treatment levels, both groups had significantly increased levels of BMD(both P<0.05), which were markedly higher in the observation group(P<0.05). Furthermore, improvement was achieved in cognitive ability and lifestyle in the observation group(both P<0.05). Conclusions Health education intervention can effectively improve BMD in elderly patients with osteoporosis, significantly improve lifestyle, and play an important role in integrated management of osteoporosis. Key words: Osteoporosis; Health education

Pharmacological Therapy of Osteoporosis: A Systematic Current Review of Literature.

Osteoporosis is the most common bone disease affecting millions of people worldwide, particularly in elderly or in post-menopausal women. The pathogenesis is useful to understand the possible mechanism of action of anti-osteoporotic drugs. Early diagnosis, possible with several laboratory and instrumental tests, allows a major accuracy in the choice of anti-osteoporosis drugs. Treatment of osteoporosis is strictly related to severity of pathology and consists on prevention of fragility fractures with a correct lifestyle and adequate nutritional supplements, and use of pharmacological therapy, started in patients with osteopenia and history of fragility fracture of the hip or spine. The purpose of this review is to focus on main current pharmacological products to treat osteoporotic patients.

Age- and gender-specific epidemiology, treatment patterns, and economic burden of osteoporosis and associated fracture in Taiwan between 2009 and 2013.

This nationwide study investigated the epidemiology, treatment patterns, and economic burden of osteoporosis and associated fracture between 2009 and 2013 in Taiwan. We used the National Health Insurance Research Database as our data source. The prevalence of diagnosed osteoporosis and major osteoporotic fractures was calculated annually from 2009 to 2013, stratified by age and gender. Osteoporosis patients who received any prescription of anti-osteoporosis drugs during each fiscal year were defined as osteoporosis patients under treatment. Healthcare utilization and associated direct medical costs were used to quantify the economic burden of osteoporosis. For patients who encountered major osteoporotic fracture, the incremental changes of direct medical costs attributable to fracture using a pre- and post-quasi-experimental design were estimated. Furthermore, we compared the annual direct medical costs of patients who encountered major osteoporotic fracture with those diagnosed osteoporosis only and with the general population. The prevalence of diagnosed osteoporosis increased with age, with the highest rate among those aged 80 and older. Overall, less than one-third of women and only 10% of men received anti-osteoporosis drugs among osteoporosis patients. The annual direct medical costs for osteoporosis patients increased steadily from 2009 to 2013. The total medical costs and incremental change of direct medical costs were higher in men than those in women. We found the treatment of osteoporosis to be alarmingly suboptimal, considering the significantly increased economic burden of major osteoporotic fracture also identified in this study. Osteoporosis men received lesser anti-osteoporosis drugs but had higher incremental costs attributable to major osteoporotic fractures.

Anti-receptor activator nuclear factor κ-B ligand (anti-RANKL) as an antiresorptive agent for renal failure osteoporotic patient

Implication for health policy/practice/research/medical education Treatment for renal failure, especially those who undergo dialysis, is very difficult and challenging. Bisphosphonates have been administered for the treatment of osteoporosis for many years, but they are administered with caution in those who have renal failure. With the introduction of Prolia as an anti-osteoporosis drug, the hope was created to treat patients with kidney failure.

Globular adiponectin reverses osteo-sarcopenia and altered body composition in ovariectomized rats

Adiponectin regulates various metabolic processes including glucose flux, lipid breakdown and insulin response. We recently reported that adiponectin receptor1 (adipoR1) activation by a small molecule reverses osteopenia in leptin receptor deficient db/db (diabetic) mice. However, the role of adiponectin in bone metabolism under the setting of post-menopausal (estrogen-deficiency) osteopenia and associated metabolic derangements has not been studied. Here, we studied the therapeutic effect of the globular form of adiponectin (gAd), which is predominantly an adipoR1 agonist, in aged ovariectomized (OVX) rats and compared it with standard-of-care anti-osteoporosis drugs. In OVX rats with established osteopenia, gAd completely restored BMD and load bearing capacity and improved bone quality. Skeletal effects of gAd were comparable to PTH (osteoanabolic) but better than alendronate (anti-catabolic). Both osteoanabolic and anti-catabolic mechanisms led to the anti-osteoporosis effect of gAd. In cultured osteoblasts and bones, gAd increased a) adipoR1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) expression to promote mitochondrial respiration, which likely fueled osteoblast differentiation, b) suppressed sclerostin (a wnt antagonist) in a sirtuin1-dependent manner and c) decreased receptor-activator of nuclear factor κB ligand (RANKL) to achieve its anti-catabolic effect. The OVX-induced sarcopenia and insulin resistance were also improved by gAd. We conclude that gAd has therapeutic efficacy in estrogen deficiency-induced osteoporosis, sarcopenia and insulin resistance and hold metabolic disease modifying potential in postmenopausal women.

One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study.

The purpose of this study was to estimate real-world persistence amongst incident users of anti-osteoporosis medications. This is a retrospective cohort using data from anonymised records and dispensation data ( www.sidiap.org ). Eligibility comprised the following: women aged ≥50, incident users of anti-osteoporosis medication (2012), with data available for at least 12months prior to therapy initiation. Exclusions are other bone diseases/treatments and uncommon anti-osteoporosis drugs (N<100). Follow-up was from first pharmacy dispensation until cessation, end of study, censoring or switching. Outcomes are 2- and 1-year persistence with a permissible gap of up to 90days. Persistence with alendronate was compared to other bisphosphonates, strontium ranelate, selective oestrogen receptor modulators, teriparatide and denosumab. Cox models were used to estimate hazard ratios of therapy cessation according to drug used after adjustment for age, sex, BMI, smoking, alcohol drinking, Charlson co-morbidity index, previous fractures, use of anti-osteoporosis medication/s, oral corticosteroids and socio-economic status. A total of 19,253 women were included. Unadjusted 2-year persistence [95% CI] ranged from 10.3% [9.1-11.6%] (strontium ranelate) to 45.4% [43.1-47.8%] (denosumab). One-year persistence went from 35.8% [33.9%-37.7%] (strontium ranelate) to 65.8% [63.6%-68.0%] (denosumab). At the end of the first year and compared to alendronate users, both teriparatide and denosumab users had reduced cessation risk (adjusted HR 0.76, 95% CI 0.67-0.86 and 0.54, 95% CI 0.50-0.59 respectively) while at the end of the second year, only denosumab had a lower risk of discontinuation (adjusted HR 0.60, 95% CI 0.56-0.64). Unadjusted 2-year persistence is suboptimal. However, both teriparatide and denosumab users had better 1-year persistence and only denosumab had 2-year better persistence compared to alendronate users. Unmeasured confounding by indication might partially explain our findings.