UNASSIGNED: Reduced bone mineral density (BMD) and microarchitectural deterioration contribute to increased fracture risk. Although the effects of anti-fracture medications (AFMs) on BMD are well-documented, their impact on bone material properties (BMPs) remains poorly characterized. Accordingly, we conducted a systematic review and meta-analysis to evaluate the effects of AFMs on BMPs. Based on data availability, we further categorized AFMs into anti-resorptives, bisphosphonates alone, and strontium ranelate subgroups to perform additional analyses of BMPs in osteoporotic patients.
UNASSIGNED: We did a comprehensive search of three databases, namely, PubMed, Web of Science, and Google Scholar, using various permutation combinations, and used Comprehensive Meta-Analysis software to analyze the extracted data.
UNASSIGNED: The 15 eligible studies (randomized and non-randomized) compared the following: (1) 301 AFM-treated patients with 225 on placebo; (2) 191 patients treated with anti-resorptives with 131 on placebo; (3) 86 bisphosphonate-treated patients with 66 on placebo; and (4) 84 strontium ranelate-treated patients with 70 on placebo. Pooled analysis showed that AFMs significantly decreased cortical bone crystallinity [standardized difference in means (SDM) -1.394] and collagen maturity [SDM -0.855], and collagen maturity in cancellous bone [SDM -0.631]. Additionally, anti-resorptives (bisphosphonates and denosumab) significantly increased crystallinity [SDM 0.387], mineral-matrix ratio [SDM 0.771], microhardness [SDM 0.858], and contact hardness [SDM 0.952] of cortical bone. Anti-resorptives increased mineral-matrix ratio [SDM 0.543] and microhardness [SDM 0.864] and decreased collagen maturity [SDM -0.539] in cancellous bone. Restricted analysis of only bisphosphonate-treated studies showed a significant decrease in collagen maturity [SDM -0.650] in cancellous bone and an increase in true hardness [SDM 1.277] in cortical bone. In strontium ranelate-treated patients, there was no difference in BMPs compared to placebo.
UNASSIGNED: Collectively, our study suggests that AFMs improve bone quality, which explains their anti-fracture ability that is not fully accounted for by increased BMD in osteoporosis patients.

Background and Objectives: Osteoporotic vertebral compression fractures (OVCFs) are prevalent among the elderly, often leading to significant pain, morbidity, and mortality. Effective management of underlying osteoporosis is essential to prevent subsequent fractures. This study aimed to compare the clinical and radiographic outcomes of teriparatide and denosumab treatments in patients with OVCFs to determine their relative effectiveness in improving patient outcomes. Materials and Methods: This retrospective study included 78 patients diagnosed with an acute thoracolumbar OVCF who received either teriparatide (35 patients) or denosumab (43 patients) within three months of a fracture. Clinical outcomes were assessed using the visual analog scale (VAS) for back pain, Oswestry disability index (ODI), and EQ-5D quality of life scores at baseline, 6 months, and 12 months. Bone mineral density (BMD) and radiographic outcomes were evaluated initially and at 12 months post-treatment. Results: Both treatment groups demonstrated significant improvements in VAS, ODI, and EQ-5D scores over 12 months. No significant differences were observed between the teriparatide and denosumab groups in terms of clinical outcomes or radiographic measurements at any time point. Fracture union and BMD improvements were similarly observed in both groups. The teriparatide group had a lower baseline BMD, but this did not affect the overall outcomes. Conclusions: Both teriparatide and denosumab are effective in improving clinical and radiographic outcomes in patients with OVCFs. Despite concerns about denosumab\'s potential to hinder fracture healing, our study found no significant differences between the two treatments. These findings support the use of denosumab for early treatment of OVCFs to prevent subsequent fractures without compromising fracture healing. Further prospective studies are needed to confirm these results.

Bisphosphonates are widely used for the treatment of postmenopausal osteoporosis; however, they cause several long-term side effects, necessitating the investigation of local ways to improve osseointegration in compromised bone tissue. The purpose of this study was to evaluate peri-implant bone repair using implants functionalized with zoledronic acid alone (OVX ZOL group, n = 11), zoledronic acid + teriparatide (OVX ZOL + TERI group, n = 11), and zoledronic acid + ruterpy (OVX ZOL + TERPY group, n = 11) compared to the control group (OVX CONV, n = 11). Analyses included computer-assisted microtomography, qualitative histologic analysis, and real-time PCR analysis. Histologically, all functionalized surfaces improved peri-implant repair, with the OVX ZOL + TERI group standing out. Similar results were found in computerized microtomography analysis. In real-time PCR analysis, however, the OVX ZOL and OVX ZOL + TERPY groups showed better results for bone formation, with the OVX ZOL + TERPY group standing out, while there were no statistical differences between the OVX CONV and OVX ZOL + TERI groups for the genes studied at 28 postoperative days. Nevertheless, all functionalized groups showed a reduced rate of bone resorption. In short, all surface functionalization groups outperformed the control group, with overall better results for the OVX ZOL + TERI group.

Osteoporosis and low bone mineral density (BMD) pose significant challenges in adult spinal deformity surgery, increasing the risks of complications such as vertebral compression fractures, hardware failure, proximal junctional kyphosis/failure, and pseudoarthrosis. This narrative review examines the current evidence on bone health optimization strategies for spinal deformity patients. Preoperative screening and medical optimization are crucial, with vitamin D supplementation showing particular benefit. Among the pharmacologic agents, bisphosphonates demonstrate efficacy in improving fusion rates and reducing hardware-related complications, though the effects may be delayed. Teriparatide, a parathyroid hormone analog, shows promise in accelerating fusion and enhancing pedicle screw fixation. Newer anabolic agents like abaloparatide and romosozumab require further study but show potential. Romosozumab, in particular, has demonstrated significant improvements in lumbar spine BMD over a shorter duration compared to other treatments. Surgical techniques like cement augmentation and the use of larger interbody cages can mitigate the risks in osteoporotic patients. Overall, a multifaceted approach incorporating medical optimization, appropriate pharmacologic treatment, and tailored surgical techniques is recommended to improve outcomes in adult spinal deformity patients with compromised bone quality. Future research should focus on optimizing the treatment protocols, assessing the long-term outcomes of newer agents in the spine surgery population, and developing cost-effective strategies to improve access to these promising therapies.

UNASSIGNED: Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use.
UNASSIGNED: To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference.
UNASSIGNED: FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals.
UNASSIGNED: Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%).
UNASSIGNED: Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide\'s clinical use.

Pregnancy and lactation-associated osteoporosis (PLO) is one of the rarest and most serious primary osteoporotic conditions that develops during the third trimester of gestation and/or early postpartum period. A history of PLO often causes individuals to hesitate when considering an additional child due to anxiety about recurrence risk. Reported here are details of a 29-year-old patient with PLO given aggressive treatment for osteoporosis with teriparatide who subsequently gave birth to a healthy child at age 33 without PLO recurrence. Further case studies are needed to examine the efficacy and safety of PLO treatment and to provide beneficial results for those who wish to have another pregnancy.

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency.

UNASSIGNED: Teriparatide, an osteoanabolic agent similar to parathyroid hormone in properties, is used to manage severe osteoporosis. Aortic valve stenosis is a common valve condition observed in the elderly. Its natural history includes gradual progression toward severity. We present a case of a patient who had rapidly progressive aortic stenosis after teriparatide initiation.
UNASSIGNED: An 84-year-old woman who was diagnosed with osteoporosis was treated with oral bisphosphonates. When she had spinal compression fractures, she was found to have primary hyperparathyroidism. She underwent parathyroidectomy and was treated with denosumab infusions every 6 months. However, after she experienced bilateral atypical femoral fractures, she was switched to teriparatide daily injections. Her laboratory test results showed a calcium level of 10 mg/dL (reference range, 8.5-10.2 mg/dL), 25-hydroxyvitamin D level of 38.2 ng/mL (reference range, 31.0-80.0 ng/mL), and phosphorus level of 3.3 mg/dL (reference, range, 2.7-4.8 mg/dL). On reviewing echocardiograms before and after teriparatide initiation, we found a rapid progression of her aortic stenosis from moderate to severe based on the mean gradients (23 to 40 mm Hg) and peak velocities (3.09 to 4 m/s), over a span of 10 months. She eventually required valve replacement.
UNASSIGNED: Natural progression of mild to severe aortic stenosis typically occurs at the rate of 3 to 7 mm Hg per year over several years. Chronic exposure of human valvular endothelial cells to parathyroid hormone can trigger endothelial dysfunction and valvular calcification.
UNASSIGNED: In patients with preexisting aortic stenosis, coordination of care with cardiology and echocardiographic monitoring while on therapy may be considered.

In this study, we used a bioinformatic approach to construct a miRNA-target gene interaction network potentially involved in the anabolic effect of parathyroid hormone analogue teriparatide [PTH (1-34)] on osteoblasts. We extracted a dataset of 26 microRNAs (miRNAs) from previously published studies and predicted miRNA target interactions (MTIs) using four software tools: DIANA, miRWalk, miRDB, and TargetScan. By constructing an interactome of PTH-regulated miRNAs and their predicted target genes, we elucidated signaling pathways regulating pluripotency of stem cells, the Hippo signaling pathway, and the TGF-beta signaling pathway as the most significant pathways in the effects of PTH on osteoblasts. Furthermore, we constructed intersection of MTI networks for these three pathways and added validated interactions. There are 8 genes present in all three selected pathways and a set of 18 miRNAs are predicted to target these genes, according to literature data. The most important genes in all three pathways were BMPR1A, BMPR2 and SMAD2 having the most interactions with miRNAs. Among these miRNAs, only miR-146a-5p and miR-346 have validated interactions in these pathways and were shown to be important regulators of these pathways. In addition, we also propose miR-551b-5p and miR-338-5p for further experimental validation, as they have been predicted to target important genes in these pathways but none of their target interactions have yet been verified. Our wet-lab experiment on miRNAs differentially expressed between PTH (1-34) treated and untreated mesenchymal stem cells supports miR-186-5p from the literature obtained data as another prominent miRNA. The meticulous selection of miRNAs outlined will significantly support and guide future research aimed at discovering and understanding the crucial pathways of osteoanabolic PTH-epigenetic effects on osteoblasts. Additionally, they hold potential for the discovery of new PTH target genes, innovative biomarkers for the effectiveness and safety of osteoporosis-affected treatment, as well as novel therapeutic targets.

OBJECTIVE: To analyze osteoporosis medication prescribing trends across specialties in the context of a Bone Health Clinic.
BACKGROUND: Osteoporosis affects over 10 million adults in the US, taking a significant toll on patients and the healthcare system. Although screening methods and treatments are improving, the disease remains underdiagnosed and undertreated. This study aims to evaluate the prescribing trends of osteoporosis medication among department specialties to delineate the benefits of a bone health clinic.
METHODS: Retrospective data collection identified and analyzed patients within the Penn State Health system prescribed one of the following osteoporosis medications: Bisphosphonate, denosumab, romosozumab, teriparatide, abaloparatide, or raloxifene. Date range: 4/18/2016 to 4/14/2021. Data collection identified the specialty origin of prescriptions for osteoporosis medications across various medical specialties (e.g., orthopaedics, family medicine, and internal medicine).
RESULTS: 10,736 prescription orders were issued to patients with an average age of 68 years. Non-Hispanic Caucasian patients received 88.6% of prescriptions, followed by Asian (3.4%) and African American (2.2%). Female patients accounted for 87.8% of all prescriptions. The Bone Health Clinic under two orthopaedic providers wrote 3,619 prescriptions, averaging 361.9 prescriptions per provider per year-marking the highest rate among specialties. The clinic prescriptions constituted 33.7% of all prescriptions across specialties. Orthopaedic surgery prescribed the most denosumab, romosozumab, teriparatide, and abaloparatide prescriptions, and had the highest number of male osteoporosis patients compared to other specialties (15.6%), consequently prescribing the most male prescriptions (578).
CONCLUSIONS: Establishing a bone health clinic dedicated to osteoporosis management leads to significantly higher prescription rates per provider, increased utilization of anabolic therapies compared to other specialties, and more male patients being treated-an often-neglected population in osteoporosis.