Pharmacological Treatment Of Osteoporosis Research Articles

First fracture in patients with osteoporosis : How does the "fracture career" of our patients with osteoporosis begin?

Given that aprimary osteoporotic fracture can result in subsequent fractures and that the precise etiology of the typical fracture cascade remains uncertain, it is pertinent to determine the initiating factor and the specific fracture involved in this cascade. All patients with afracture of along bone were consecutively screened over the 12-month study period. All participants were asked about existing risk factors (including previous fractures) in accordance with the applicable guidelines of the Umbrella Organization Osteology (DVO). The existing risk factors were employed to calculate the fracture risk and this formed the basis of the diagnosis and indications for treatment. Atotal of 613 patients were included in the study. Of the total number of patients 378 were deemed to require pharmacological treatment for osteoporosis. In this cohort 182 fractures were reported. Among the previous fractures distal radius fractures were the most common, occurring in 54patients followed by fractures of the proximal femur (n = 40) and proximal humerus (n = 27). As anticipated, abreakdown of the data by gender revealed adifferent picture. In line with the incidences it can be seen that men have fewer distal radius fractures and more fractures close to the hip joint. The results indicate that women with adistal radius fracture have the potential to facilitate an early diagnosis and subsequent treatment for osteoporosis. In contrast, in men fractures in the region of the hip joint were the most common initial presentation, precluding the possibility of deriving an early indication of the presence of osteoporosis from previous fractures.

Bisphosphonate Use in Patients Who Have Osteoporosis Does Not Increase the Risk of Periprosthetic Fracture Following Total Knee Arthroplasty

BackgroundThe purpose of this study was to evaluate the effect of preoperative bisphosphonate use in patients who have osteoporosis on the risk of complications following primary total knee arthroplasty (TKA). MethodsAn administrative claims database was queried for patients who have osteoporosis undergoing primary TKA between 2010 and 2019 with a minimum of 2-year follow-up. Bisphosphonate-naive patients and bisphosphonate users, defined as patients who had a continuous prescription for bisphosphonates for a minimum of 6 months preoperatively, were matched 1:1 based on age, sex, and comorbidity burden. Patients undergoing nonelective TKA on chronic glucocorticoid therapy or receiving any other pharmacologic treatment for osteoporosis were excluded. The final cohort included 21,058 matched pairs of patients. The incidence of postoperative complications was identified via International Classification of Disease coding and compared between matched groups. A subgroup analysis was performed to examine outcomes among patients who underwent cemented and cementless TKA. ResultsThere was no difference in the incidence of periprosthetic fracture on univariate (0.7 versus 0.8%, P = 0.068) or multivariate testing (OR [odds ratio]: 1.24, 95% confidence interval [0.99 to 1.56]; P = 0.060). Bisphosphonate users were statistically less likely to undergo all-cause revision TKA at 2 years (OR: 0.84 [0.72 to 0.97]; P = 0.021). Patients who had osteoporosis were found to have an increased risk of periprosthetic fracture when TKA was performed with cementless implants (1.6 versus 0.4%; P = 0.033). However, when treated with bisphosphonates, patients who have osteoporosis demonstrated equivalent fracture rates regardless of implant type (1.3 versus 1.0%; P = 1.000). ConclusionsWhile bisphosphonate use in patients who have osteoporosis did not decrease the risk of periprosthetic fracture, it did significantly lower the incidence of all-cause revision at 2 years, although the difference identified was small. Consideration should be given to performing cemented TKA in patients who have untreated osteoporosis, given the higher rate of periprosthetic fracture when cementless implants were utilized.

Physician-dentist dual referral model concept for coordinated bone anabolic therapy

BackgroundBone anabolic drugs used for the pharmacologic treatment of osteoporosis have the potential to enhance alveolar bone regeneration to improve implant success. There are no US Food and Drug Administration–approved drugs indicated to improve oral bone density around teeth or implants. MethodsThe authors summarized expert opinions on a novel coordinated treatment approach leveraging the effects of systemic bone anabolic drugs to enhance dental implant therapy in patients with osteoporosis and a dual referral model for physicians and dentists to address the clinical needs of patients with osteoporosis from a comprehensive perspective of oral-systemic health. Interviews of key opinion leaders were conducted with a bone health specialist group consisting of specialists in orthopedic surgery, internal medicine, geriatrics, endocrinology, and clinical densitometry and a surgical dental specialist group consisting of periodontists and oral surgeons. ResultsOverall, both groups shared positive feedback on the idea of strategically timing administration of anabolic osteoporosis drugs with dental treatment. Both groups expressed interest in the dual referral model. ConclusionsThe feedback of key opinion leaders supported the coordinated bone anabolic therapy concept and identified a need for improved interdisciplinary collaboration, education, and communication to realize the synergies of physician-dentist clinical cooperation. Practical ImplicationsStrategic timing of osteoporosis therapy could improve skeletal bone health and reduce fracture risk while offering adjunctive dental benefits.

Osteoporosis treatment: current drugs and future developments.

Osteoporosis is a common systemic metabolic disease characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility. Pharmacological treatment of osteoporosis is the focus of current research, and anti-osteoporosis drugs usually play a role in inhibiting bone resorption, promoting bone formation, and having a dual role. However, most of the drugs have the disadvantages of single target and high toxic and side effects. There are many types of traditional Chinese medicines (TCM), from a wide range of sources and mostly plants. Herbal plants have unique advantages in regulating the relationship between osteoporosis and the immune system, acupuncture therapy has significant therapeutic effects in combination with medicine for osteoporosis. The target cells and specific molecular mechanisms of TCM in preventing and treating osteoporosis have not been fully elucidated. At present, there is a lack of comprehensive understanding of the pathological mechanism of the disease. Therefore, a better understanding of the pathological signaling pathways and key molecules involved in the pathogenesis of osteoporosis is crucial for the design of therapeutic targets and drug development. In this paper, we review the development and current status of anti-osteoporosis drugs currently in clinical application and under development to provide relevant basis and reference for drug prevention and treatment of osteoporosis, with the aim of promoting pharmacological research and new drug development.

Expert opinion on the management of patients with osteoporosis with anabolic drugs in Italy.

Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

Osteoporosis treatments for intervertebral disc degeneration and back pain: a perspective.

Low back pain derived from intervertebral disc (IVD) degeneration is a debilitating spinal condition that, despite its prevalence, does not have any intermediary guidelines for pharmacological treatment between palliative care and invasive surgery. The development of treatments for the IVD is complicated by the variety of resident cell types needed to maintain the regionally distinct structural properties of the IVD that permit the safe, complex motions of the spine. Osteoporosis of the spine increases the risk of vertebral bone fracture that can increase the incidence of back pain. Fortunately, there are a variety of pharmacological treatments for osteoporosis that target osteoblasts, osteoclasts and/or osteocytes to build bone and prevent vertebral fracture. Of particular note, clinical and preclinical studies suggest that commonly prescribed osteoporosis drugs like bisphosphonates, intermittent parathyroid hormone, anti-sclerostin antibody, selective estrogen receptor modulators and anti-receptor activator of nuclear factor-kappa B ligand inhibitor denosumab may also relieve back pain. Here, we cite clinical and preclinical studies and include unpublished data to support the argument that a subset of these therapeutics for osteoporosis may alleviate low back pain by also targeting the IVD.

Pharmacolgic osteoporosis treatment of nursing home residents

Fragility fractures in older people are common and are often associated with nursing home admission in frail people. Only few institutionalized residents with documented osteoporosis receive pharmacologic osteoporosis treatment. Studies demonstrating the benefit of osteoporosis drug therapy in this multimorbid and vulnerable population are lacking.

Oxyresveratrol attenuates bone resorption by inhibiting the mitogen-activated protein kinase pathway in ovariectomized rats

BackgroundBone is continuously produced by osteoblasts and resorbed by osteoclasts to maintain homeostasis. Impaired bone resorption by osteoclasts causes bone diseases such as osteoporosis and arthritis. Most pharmacological treatment of osteoporosis focuses on inhibiting osteoclast differentiation, often to restore osteoclast/osteoclast balance. However, recent osteoporosis treatments have various side effects. According to a recent study, resveratrol, known as a stilbenoid family, is known to increase bone density, and the osteoclast inhibitory effect was confirmed using oxyresveratrol, a stilbenoid family. Here, we investigated the effect of oxyresveratrol on osteoclast differentiation and an ovariectomized mouse model.MethodsMouse leukemia monocyte/macrophage cell line RAW 264.7 was treated with oxyresveratrol, and cell cytotoxicity was confirmed by measuring MTT assay. Tartrate-resistant acid phosphatase (TRAP), an enzyme marker for osteoclasts, was confirmed by staining. In addition, osteoclast differentiation markers and MAPK-related markers were confirmed at the mRNA level and protein expression. The effect of oxyresveratrol was confirmed using ovariectomized mice. Deoxypyridinoline (DPD) was measured using mouse urine and TRAP activity was observed using serum. Bone mineral density was also measured using Micro-CT.ResultsThe polyphenol oxyresveratrol inhibited receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells. Furthermore, oxyresveratrol inhibited TRAP activity and actin-ring formation. Moreover, oxyresveratrol suppressed the phosphorylation of the RANKL-induced mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK and significantly reduced the expression of bone differentiation markers (NFATc1, cathepsin K, and TRAP).ConclusionOxyresveratrol inhibits osteoclast differentiation via MAPK and increases bone density in ovariectomized rats, suggesting it has therapeutic potential for bone diseases such as osteoporosis. We confirmed the osteoporosis prevention effect of OR in Raw 264.7 cells, and future studies should confirm the effect of OR using rat bone marrow-derived cells.

The Portuguese state of the art on osteoporosis and fracture risk: an update on the treatment options

AbstractOsteoporosis and fragility fractures are serious public health problems, which greatly impact individual health and the economy of other health services. Pharmacological treatment is still one of the main elements of clinical intervention, combined with non-pharmacological measures, in preventing the occurrence of fragility fractures. The emergence of promising new pharmacological options in the treatment of osteoporosis seems to renew expectations in the prevention of complications and a subsequent reduction in morbidity and mortality, including symptomatic treatment, improved physical function and a better quality of life. This review aims to provide updated information on the pharmacological treatment of osteoporosis in the adult population. A comprehensive PubMed search was performed to review the current evidence on osteoporosis treatment. Of the 378 articles identified from the initial queries, the final review included 80 articles. Currently, the following pharmacological options are available: antiresorptive (bisphosphonates, denosumab, postmenopausal hormone replacement therapy and selective oestrogen receptor modulators), bone-forming agents (essentially, teriparatide and abaloparatide) and the new dual-action therapy (romosozumab), recently approved by the US Food and Drug Administration and the European Medicines Agency, but which is not yet an option in Portugal. Therapeutic selection is essentially based on assessment of cost-effectiveness, since current evidence does not suggest any differences between the distinctive classes in reducing the risk of fractures, but this analysis is limited by the scarcity of comparative intraclass studies. Notwithstanding, romosozumab, as a dual effect therapy, is promising in resolving the physiological limitations resulting from the merely unilateral action of antiresorptive agents and bone-forming agents in the inseparable relationship between bone formation and resorption. However, its cardiovascular safety raises some concerns, and this topic is still being debated. The underdiagnosis and the undertreatment of osteoporosis remain one of the greatest challenges of the 21st century. Over the years, new drugs have appeared that have tried to address these problems with a direct impact on the health of populations, but a long way remains to be come in optimising their effectiveness, safety and tolerability.

Post-Fracture Care Program: Pharmacological Treatment of Osteoporosis in Older Adults with Fragility Fractures.

To present and discuss the recently published scientific evidence on the approach, mode of action, and timing of osteoporosis therapy initiation after fragility fractures. A comprehensive management approach is required to reduce mortality and morbidity associated with fragility fractures. This will help to reduce the risk of missing the diagnosis of osteoporosis as the underlying disorder while at the same time promoting the timely treatment of osteoporosis. The target is to minimize the incidence of post-traumatic disability and to reduce the imminent fracture risk. This article will present a Bone-Care algorithm for the diagnosis and management of fragility fractures in patients presenting for trauma surgery. This algorithm has been developed based on recently published national as well as international guidelines for implementation in standard clinical practice. International figures revealed that only a small proportion of those patients at high risk of sustaining a fragility fracture receive osteoporosis therapy. Based on the best currently available evidence, it is safe to start osteoporosis therapy in the acute post-fracture period (the optimal therapeutic window of romosozumab is the late endochondral phase/throughout bone remodeling). The right Bone-Care pathway ensures the delivery of a comprehensive management approach that meets the global call to action. All parameters including risk, benefit, compliance, and cost should be considered on an individual base for all kinds of therapy.

Osteoporosis: Spotlight on current approaches to pharmacological treatment.

Despite the availability of safe and effective anti-osteoporosis treatments, osteoporosis continues to be undertreated. The increase in fragility fractures, which is the main clinical consequence of osteoporosis, is a major problem for healthcare systems of countries. A broad range of drugs including antiresorptive and anabolic agents are used in the pharmacological treatment of osteoporosis. Fracture risk assessment in drug selection is of utmost importance in terms of guiding treatment. The recommended thresholds for osteoporosis treatment decision making are based on major osteoporotic and hip fracture probabilities from the Fracture Risk Assessment Tool (FRAX®). Currently, antiresorptive agents are usually the first choice to increase bone mineral density (BMD) and reduce the fracture risk. Bisphosphonates and antiresorptive drugs such as denosumab, a nuclear factor kappa-B ligand (RANKL) inhibitor, are the most widely used drugs in the treatment of osteoporosis. Bisphosphonates alone are unlikely to provide long-term protection against fracture and restore BMD in patients with severe osteoporosis and high fracture risk. In such patients, treatment with an anabolic agent such as teriparatide, abaloparatide, or romosozumab should be ideally initiated to achieve maximal gain in bone mass and preserve the microarchitecture. Ideally, an antiresorptive drug should be continued to maintain gain in bone mass.

Recommendations for the Pharmacological Treatment of Osteoporosis – Update 2023 of the German Osteoporosis Guideline

Abstract Aim The German osteoporosis guideline was updated on the basis of a systematic literature review and through a structured consensus process by an interdisciplinary, international (Germany, Austria, Switzerland) expert group representing the 20 member societies of the Joint Osteological Association (DVO) and patient advocacy organizations (BfO). This manuscript summarizes the changes in the German osteoporosis guideline with regard to pharmacological interventions and offers pragmatic pathways for implementation. Method Systematic literature search and structured consensus building according to AWMF regulations. Results The sclerostin antibody romosozumab was adopted into the guideline. In addition, the effectiveness of teriparatide was re-evaluated. For both bone anabolic agents evidence from randomized trials underlined a superiority over oral bisphosphonates with regard to fracture risk reduction. Between the antiresorptive treatments, differences regarding superiority/inferiority could only be shown with respect to surrogate parameters, not with regard to fractures. Data about the duration of treatment of all available drugs is limited. All non-bisphosphonate treatments require follow-up treatment. Conclusion An individualized treatment concept should be developed in a shared decision process, including a bone anabolic-first strategy in high-risk patients. Recommendations on treatment duration, drug holidays and sequential strategies should be considered.

Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Trials.

Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long-term fracture risk. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen-containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta-analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%-5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%-3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%-2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%-6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%-5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%-5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N-telopeptide (-52.2%, 95% CI -60.3% to -44.2%, p < 0.00001, n = 3 studies) and bone-specific alkaline phosphatase (-34.2%, 95% CI -42.6% to -25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta-analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Integrating post-fracture care into the primary care setting (interFRACT): Protocol for a mixed-methods study to co-design a care program to improve rates of osteoporosis and fracture treatment

IntroductionDespite evidence showing that timely diagnosis and appropriate pharmacological treatment of osteoporosis reduces subsequent fracture rates, osteoporosis remains significantly underdiagnosed and undertreated. The large and ongoing treatment gap for osteoporosis...

Influence of the Osteogenomic Profile in Response to Alendronate Therapy in Postmenopausal Women with Osteoporosis: A Retrospective Cohort Study.

Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do not respond adequately to therapy with alendronate. The aim of this work was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with response to anti-osteoporotic treatment in postmenopausal women with primary osteoporosis. A total of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year were observed. The bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change, patients were divided into two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ESR1, IL-6, PTHR1, TGFβ, OPG and RANKL genes were determined and profiles were generated from the combination of risk alleles. A total of 56 subjects were responders to alendronate and 26 subjects were non-responders. Carriers of the G-C-G-C profile (constructed from rs700518, rs1800795, rs2073618 and rs3102735) were predisposed to response to alendronate treatment (p = 0.001). Our findings highlight the importance of the identified profiles for the pharmacogenetics of alendronate therapy in osteoporosis.

Exploring the osteoporosis treatment gap after fragility hip fracture at a Tertiary University Medical Center in Thailand

Background(1) To evaluate the prescription rate of anti-osteoporosis medication, and (2) to identify factors associated with patients not receiving anti-osteoporosis medication or, when prescribed, not persisting with medication 1 year after hip fracture treatment.MethodsWe retrospectively reviewed the medical records of all fragility hip fracture patients admitted to the orthopedic unit of the Faculty of Medicine Siriraj Hospital, Mahidol University, between July 1, 2016, and December 31, 2019. We identified patients who did not receive anti-osteoporosis medication both 6 months and 1 year after fracture treatment. Patients who did not receive the medication 1 year after their treatment were enrolled and interviewed using a no-treatment questionnaire.ResultsIn total, 530 patients with fragility hip fractures were eligible (mean age, 79.0 years), and most (74.5%) were women. Only 148 patients (31.6%) received anti-osteoporosis medication 1 year after hip fracture. Logistic regression analysis identified predictors for not receiving the medication: male sex (OR 1.8; 95% CI 1.1–3.0), Charlson comorbidity index score ≥ 5 (OR 1.5; 95% CI 1.0–2.3), and secondary school education or below (OR 2.0; 95% CI 1.2–3.3). The main reason for not receiving the medication was that healthcare providers neither discussed nor initiated pharmacological treatment for osteoporosis (48.2%). When the medication was prescribed, non-persistence primarily stemmed from transportation difficulties that resulted in patients missing follow-ups (50.0%).ConclusionsImproved physician attitudes toward anti-osteoporosis medications might enhance the treatment rate. Developing a follow-up team and facilitating access to medications (eg, courier delivery to patients) would promote therapy compliance.Trial registrationsThe protocol for the first phase and second phase was approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021) and for the second phase, patients-informed consent forms used in the cross-sectional component were approved by the Siriraj Institutional Review Board of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand (COA no. Si 180/2021). The research was registered with the Thai Clinical Trials Registry (TCTR number: 20210824002). The study was conducted in accordance with the Declaration of Helsinki. Each patient (or a relative/caregiver) provided informed consent in writing or by telephone to participate in this second study phase.

Annals for Educators - February 2023.

Annals for Educators - February 2023.

Possible early detection of prodromal bone marrow edema in atypical femoral fracture associated with denosumab by fat-suppressed proton density mri - a case report

&lt;p&gt;背景和目的：非典型股骨骨折(AFF)為長期以抗骨吸收藥物治療骨質疏鬆相關的嚴重不良事件。過往文章多報導與AFF發生前長期使用雙膦酸鹽相關的前驅髖痛；前驅期亦可以MRI證明骨髓水腫。然地諾單抗是一種生物抗骨吸收劑；其與AFF前驅之相關特色尚未被明確描述。方法：本報告回顧分析一例68歲家庭主婦長期使用地諾單抗後發生AFF的病歷；雙膦酸鹽未開立處方亦未曾使用。結果：本例展示長期使用地諾單抗可於AFF前驅期發生骨髓水腫；此篇記錄從開始使用到發生AFF及其後續之臨床過程。結論：本病例報告強調早期發現並及時調整用藥的重要。儘管患者因缺乏預防而經歷AFF，本報告目的是提高認識；通過及時調整藥物應能預防AFF。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Background and Purpose: Atypical femoral fracture (AFF) is a severe adverse event associated with long-term use of antiresorptive agent for pharmacological treatment of osteoporosis. Many previously published articles had reported prodromal hip pain associated with long-term use of bisphosphonates before occurrence of AFF; additionally, bone marrow edema might also be demonstrated using MRI during the prodromal phase. However, denosumab, a biological antiresorptive agent, is not yet as well characterized regarding its association with prodromal phase of AFF. Methods: This report retrospectively reviewed a case of 68-year-old housewife experiencing AFF after long-term use of denosumab; bisphosphonates were never prescribed and were never used. Results: This is a case to demonstrate that bone marrow edema can occur during the prodromal phase of AFF with long-term use of denosumab; clinical course from the start of its usage until occurrence of AFF and its sequela were cap-tured. Conclusion: In this case report, crucial importance of early detection along with timely adjustment of medication is emphasized. Although the patient reported had experienced AFF due to lack of prevention, the purpose of this case report is to raise the awareness that AFF can be prevented with timely adjustment of medications.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

RF30 | PSAT138 Romosozumab-aqqg in the Treatment of Osteoporosis in a Patient with Hypophosphatasia

Abstract Background Hypophosphatasia (HPP) is a rare inherited condition that causes osteomalacia and recurrent fractures. Therapeutic options for osteoporosis in patients with concomitant HPP are limited due to concerns for a greater likelihood of atypical femoral fractures (AFF) with anti-resorptive agents such as bisphosphonates and denosumab. We present a patient with HPP and OP who was treated with the anti-sclerostin antibody romosozumab-aqqg (Romo). Clinical Case An 81-year-old female was referred for management of OP. Fracture history included a hip fracture around age 40, and bilateral metatarsal fractures around age 65. Her initial DXA scan at age 57 showed osteoporosis at the lumbar spine (LS, T-score: -2.8) and femoral neck (FN, T-score -3.2). Sequential osteoporosis treatment over the subsequent 20 years included several years of oral bisphosphonates, hormone replacement therapy, teriparatide for one year followed by two years of alendronate, and one denosumab injection. Despite almost 20 years of pharmacologic osteoporosis treatment, her bone mineral density (BMD) worsened. HPP was suspected on the basis of low serum alkaline phosphatase (AP) levels ranging from 25-37 U/L (ref: 35-104 U/L). The diagnosis was substantiated by an elevated plasma vitamin B6 level of 305 mcg/L (ref: 5-50 mcg/L) and confirmed by genetic testing showing a diagnostic missense mutation c.571G&amp;gt;A in exon 6 in the ALPL gene. After diagnosing HPP, her osteoporosis was treated with an additional year of teriparatide followed by raloxifene, which she tolerated poorly. Following two years of expectant management, during which time her BMD worsened despite calcium and vitamin D supplementation to T-scores of –4.4 at the LS, she was started on Romo. After 11 monthly injections, a follow up DXA scan showed improvements of 21%, and 10% at the LS and total hip, respectively. These changes were substantially greater than what she experienced with her first year of teriparatide therapy (+4% and +8%, respectively). Blood AP remained low on Romo (37 IU/L and 29 IU/L at 9 and 12 months post-Romo initiation). She tolerated Romo and well and experienced no fractures during treatment. Discussion Management of osteoporosis in patients with HPP is challenging, as bisphosphonates and denosumab are generally avoided due to concern for an increased risk of AFF. Case reports of patients with HPP have suggested good BMD response to teriparatide. To our knowledge, this is the first report of a patient with HPP and osteoporosis treated with Romo. In our patient, Romo did not significantly impact serum AP, but improved BMD significantly more than in response to teriparatide. In conclusion, Romo is a potential treatment option for OP in patients with HPP for whom limited alternatives exist. Optimal osteoporosis treatment following a 1-year course of Romo remains to be determined. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:05 p.m. - 1:11 p.m.

Appropriate FRAX® Intervention Threshold for Pharmacological Treatment of Osteoporosis in Thailand

Purpose: The Fracture Risk Assessment Tool (FRAX®) has been recommended and incorporated into osteoporotic guidelines worldwide to assess fracture risk and promptly diagnose osteoporosis when bone mineral density is unavailable. However, a country-specific intervention threshold for Thai patients remains unknown. Therefore, we aimed to identify an appropriate cut-off point for the 10-year probability of hip fracture (HF), specifically in the Thai population. Methods: This retrospective cohort study included members of the Thai population aged 50-90 years, enrolled from January 2018 to January 2020. Analysis of data collected from online FRAX® tool questionnaires was conducted and the receiver operating characteristic (ROC) curve was used to determine a new appropriate cut-off value as the intervention threshold. Results: A total of 1,311 (HF: 422 [32.2%], non-HF: 889 [67.8%]) participants were included. The FRAX® 10-year probability of fracture in patients with HF was significantly higher than in non-HF (5.8% ± 4% vs. 4.7% ± 4.5%, respectively; P &lt; 0.01), whereas the probability of major osteoporotic fracture (MOF) was similar (11.0 ± 5.8% vs. 10.6 ± 6.2%, P = 0.27). The ROC curve revealed a new intervention threshold for the FRAX®-based 10-year risk for HF of 4.3% with a maximum area under the curve (AUC) (95% confidence interval: 0.632 (range: 0.602-0.663; P &lt; 0.001), with sensitivity and specificity of 62.9% and 60.7%, respectively. Conclusions: The intervention threshold cut-off value for osteoporosis treatment among the Thai population was 4.3%, which is higher than the cut-off point recommended in the Thai national guidelines.