Overview of the Pharmacological Management of Osteoporosis in Postmenopausal Women

Aim: The aim of the study is to assess the Pharmacological management of osteoporosis in postmenopausal women. Objective: The purpose of this study is to evaluate the treatment of osteoporosis in postmenopausal women. Methodology: This is an observational prospective study, carried out in a tertiary care hospital. Results: A total of 300 postmenopausal women were enrolled in the study. The mean ± standard deviation, of the age of postmenopausal women included in this study was 55.5 ± 5.0 years. 68.1% were prescribed with the combinational therapy of Teriparatide+Bisphosphonates. 39.2% of subjects were using acetaminophen for pain. Conclusion: Antiresorptive drugs (hormonal therapy, bisphosphonates, and denosumab) and, the anabolic agents (teriparatide) are commonly prescribed, in this study it is obvious that Sequential Therapy is highly prevailing in the clinical practice, with 68.1%.

Recent Progresses in the Treatment of Osteoporosis

Osteoporosis (OP) is a chronic bone disease characterized by aberrant microstructure and macrostructure of bone, leading to reduced bone mass and increased risk of fragile fractures. Anti-resorptive drugs, especially, bisphosphonates, are currently the treatment of choice in most developing countries. However, they do have limitations and adverse effects, which, to some extent, helped the development of anabolic drugs such as teriparatide and romosozumab. In patients with high or very high risk for fracture, sequential or combined therapies may be considered with the initial drugs being anabolic agents. Great endeavors have been made to find next generation drugs with maximal efficacy and minimal toxicity, and improved understanding of the role of different signaling pathways and their crosstalk in the pathogenesis of OP may help achieve this goal. Our review focused on recent progress with regards to the drug development by modification of Wnt pathway, while other pathways/molecules were also discussed briefly. In addition, new observations made in recent years in bone biology were summarized and discussed for the treatment of OP.

Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption

Bone formation and resorption are typically coupled, such that the efficacy of anabolic osteoporosis treatments may be limited by bone destruction. The multi-kinase inhibitor YKL-05-099 potently inhibits salt inducible kinases (SIKs) and may represent a promising new class of bone anabolic agents. Here we report that YKL-05-099 increases bone formation in hypogonadal female mice without increasing bone resorption. Postnatal mice with inducible, global deletion of SIK2 and SIK3 show increased bone mass, increased bone formation, and, distinct from the effects of YKL-05-099, increased bone resorption. No cell-intrinsic role of SIKs in osteoclasts was noted. In addition to blocking SIKs, YKL-05-099 also binds and inhibits CSF1R, the receptor for the osteoclastogenic cytokine M-CSF. Modeling reveals that YKL-05-099 binds to SIK2 and CSF1R in a similar manner. Dual targeting of SIK2/3 and CSF1R induces bone formation without concomitantly increasing bone resorption and thereby may overcome limitations of most current anabolic osteoporosis therapies.

Antiresorptive and anabolic medications used in the perioperative period of patients with osteoporosis undergoing spine surgery: their impact on the biology of fusion and systematic review of the literature

OBJECTIVE Osteoporosis represents the most common metabolic disease of the bone, with an estimated 10% of adults aged 50 years or older affected in the United States. This patient population is at increased risk for spine fracture and instrumentation-related complications after spine surgery. Surgeon knowledge of the available treatments for patients with low bone mineral density (BMD) and how they impact biology of fusion may help mitigate negative effects in the postoperative period. Recombinant parathyroid hormone, which is sold under the name teriparatide, is the most extensively studied bone-protecting agent in humans. Additionally, the success of the monoclonal antibody denosumab has led to further clinical investigations of human patients undergoing spine surgery. Another monoclonal antibody, romosozumab, was recently approved by the US FDA for human use in patients with osteoporosis. Although studies of romosozumab in patients undergoing spine surgery have not been conducted, this is a promising potential therapeutic agent based on its early success in preclinical and clinical trials. Here, the authors aimed to review the mechanisms of action and evidence of use of antiresorptive and anabolic agents in patients with osteoporosis undergoing spine surgery. METHODS In accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted to explore the antiresorptive and anabolic agents used in the perioperative period in patients with osteoporosis undergoing spinal surgery. The search was performed by using the PubMed, Embase, and Cochrane Library databases. Titles and abstracts were screened and subsequently selected for full review. RESULTS The initial search returned 330 articles. Of these articles, 23 final articles were included and reviewed. Many of these articles reported that use of adjuvant agents in the perioperative period improved radiographic evidence of bony fusion and bone fusion rates. These agents tended to improve BMD postoperatively. CONCLUSIONS Although antiosteoporosis agents are effective to varying degrees as treatments of patients with low BMD, teriparatide and bisphosphonates have been the most extensively studied with respect to spinal instrumentation. The advent of newer agents represents an area for further exploration, especially due to the current paucity of controlled investigations. It is imperative for spine surgeons to understand the mechanisms of action of these drugs and their effects on biology of fusion.

Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis

<b><i>Background:</i></b> The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. <b><i>Objectives:</i></b> The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. <b><i>Methods:</i></b> PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran <i>Q</i> χ² test and <i>I</i>² statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). <b><i>Results:</i></b> The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35–0.53; and <i>p</i> &#x3c; 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74–0.96; and <i>p</i> = 0.009 and RR = 0.75; 95% CI = 0.58–0.97; and <i>p</i> = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00–1.02; and <i>p</i> = 0.23). <b><i>Conclusions:</i></b> Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.

Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption

Bone formation and resorption are typically coupled, such that the efficacy of anabolic osteoporosis treatments may be limited by bone destruction. The multi-kinase inhibitor YKL-05-099 potently inhibits salt inducible kinases (SIKs) and may represent a promising new class of bone anabolic agents. Here we report that YKL-05-099 increases bone formation in hypogonadal female mice without increasing bone resorption. Postnatal mice with inducible, global deletion of SIK2 and SIK3 show increased bone mass, increased bone formation, and, distinct from the effects of YKL-05-099, increased bone resorption. No cell-intrinsic role of SIKs in osteoclasts was noted. In addition to blocking SIKs, YKL-05-099 also binds and inhibits CSF1R, the receptor for the osteoclastogenic cytokine M-CSF. Modeling reveals that YKL-05-099 binds to SIK2 and CSF1R in a similar manner. Dual targeting of SIK2/3 and CSF1R induces bone formation without concomitantly increasing bone resorption and thereby may overcome limitations of most current anabolic osteoporosis therapies.