Effect of Denosumab on Bone Health, Vascular Calcification, and Health-Related Quality of Life in Hemodialysis Patients with Osteoporosis: A Prospective Observational Study.

Background: Osteoporosis is common in hemodialysis (HD) patients, contributing to cardiovascular risks. Limited research exists on denosumab's efficacy in this group. Our study explores denosumab's effects on bone turnover markers (BTMs) and vascular calcification in chronic kidney disease-mineral bone disorder (CKD-MBD) patients. Methods: In a prospective single-center study, we investigated the effects of denosumab over 2 years on 30 HD patients from a cohort of 185. Annual assessments of bone mineral density (BMD), vascular calcification, and health-related quality of life (HRQL) were conducted and compared with an untreated group. Mineral and bone parameters were analyzed at specific intervals in the treatment group. Results: Denosumab notably raised femoral BMD in the initial year. Most bone turnover markers (BTMs) decreased, except for osteocalcin. Changes in T50 correlated with BTMs. Pre-denosumab supplementation of calcium and vitamin D helped manage mineral imbalances. Post denosumab, parathyroid hormone (PTH) levels increased initially, stabilizing after 3 months. No significant changes occurred in vascular calcification or HRQL. Conclusions: Denosumab exhibited varying effects on BMD improvement, with a stronger impact in the first year that diminished in the second year. Early PTH monitoring was crucial, and extending the administrative period may enhance BMD outcomes compared to the general population.

Cancer treatment-induced bone loss.

Cancer treatment-induced bone loss (CTBL) is associated with anti-tumor treatments, including endocrine therapies, chemotherapeutic treatments, radiotherapy, glucocorticoids, and tyrosine kinase inhibitors. Osteoporosis, characterized by the loss of bone mass, can increase the risk of fractures, leading to mortality and long-term disability, even after cancer remission. Cancer and osteoporosis have marked clinical and pathogenetic similarities. Both have a multifactorial etiology, affect the geriatric population, and markedly influence quality of life. Lifestyle management, including calcium and vitamin D supplementation, is recommended but the supporting evidence is limited. Oral and injectable bisphosphonates are effective for osteoporosis and malignant bone disease. Bisphosphonates increase bone mineral density (BMD) in patients with CTBL. Denosumab is also used in the management of CTBL; in clinical trials, it improved BMD and reduced the risk of fracture. Currently, there are no bone anabolic therapies for patients with cancer. Appropriate therapies are necessary to maintain optimal bone health, particularly in patients at heightened risk.

Denosumab as treatment of central giant cell granuloma of the jaws. a scoping review.

Denosumab has been considered a treatment option for Central Giant Cell Granuloma (CGCG) a benign locally aggressive osteolytic lesion of the jaws. This study aimed to perform a scoping review of CGCG treated with Denosumab. The research question was: What is Denosumab's effectiveness in treating CGCG of the jaws? Studies that used Denosumab as a treatment for CGCGs in the jaws were selected following PRISMA-ScR guidelines, using Pubmed/Medline, Scopus, and Springer Link databases, among others. Demographics, clinical information, dosing, efficacy, adverse drug reactions (ADRs), and imaging tests used to assess the evolution of the lesions were extracted. Twenty-one studies were selected. Sixty patients with a mean age of 23.2 years were treated with Denosumab, 42% with 120 mg subcutaneously monthly, additional doses on days 1, 8, and 15 for month 1 in adults. In children, dosing was adjusted by weight to 60 or 70 mg. To avoid ADRs 500 mg of calcium and 400 IU of vitamin D orally were used. Initial effective response was reported after 1-3 months, with recurrence of 19.6% and ADRs in 74% of cases. Denosumab is effective for CGCG with monthly subcutaneous doses of 120 mg, 60 or 70 mg in patients < 45 or 50 kg for ≥ 12 months with calcium and vitamin D supplementation until remission changes are observed. Extensive or refractory lesions were the main indications. Common ADRs were hypo and hypercalcemia. Further studies are needed to define dose and supplementation protocols to avoid ADRs during and after therapy.

Sustained hypophosphatemia after denosumab in a patient on hemodialysis.

An 81-year-old Caucasian man who had commenced thrice weekly hemodialysis (HD) three months earlier, presented with a hip fracture, two vertebral fractures and a bone mineral density T-score of -3.6. He had received weekly iron sucrose infusions for 6 weeks and alphacalcidol on dialysis days. Although he suffered from coeliac disease and cirrhosis, he was fully ambulatory and well-nourished. He was normocalcaemic with a marginally low plasma phosphate and the PTH was 11.8 pmol/L (<2-times the upper range of the assay). In view of his severe osteoporosis, it was decided to treat him with denosumab (dmab). Laboratory assessment 2 weeks post dmab showed severe hypophosphatemia and hypocalcemia; phosphate 0.11 mmol/L and ionized calcium 0.83 mmol/L, and he was admitted for intravenous phosphate infusion. Three months later he remained on a phosphate supplement. The case illustrates that, in addition to the risks of hypocalcemia in patients with kidney failure and high bone turnover, kidney failure patients without evidence of high bone turnover, can also be at risk of hypocalcemia and severe hypophosphatemia requiring acute hospitalization and phosphate infusion. The potential role of compromised phosphate absorption versus increased deposition will be discussed. We recommend a cautious approach to dmab therapy in patients on dialysis, with evaluation of bone turnover and serum phosphate levels prior to initiation of treatment.

Hypocalcemia in Patients With Osteoporosis and Normal Renal Function, Treated With Denosumab, a Retrospective Analysis.

Objective: The reported hypocalcemia in postmenopausal women with osteoporosis who received Denosumab was low (0.05%-1.7% to 7.4%). The major prediction factors were vitamin D and calcium levels and renal function. The objective is to evaluate the incidence of hypocalcemia in patients with osteoporosis, normal renal function, and vitamin D who received Denosumab. Method: A retrospective analysis was conducted using the medical records (2022-2023). We looked for hypocalcemia (albumin-adjusted calcium lower than 2.2 mmol/L). Results: Two hundred one postmenopausal women diagnosed with osteoporosis and received denosumab treatment were included. All patients received vitamin D3 capsules and calcium supplementation. The mean age of the patient was 75.7 ± 7.0 years (56-91 years). Hypocalcemia was observed in 46 (23%) patients following a subcutaneous dose of Denosumab 60 mg. Median calcium was 2.25 mmol/L (minimum: 0.890 mmol/L, maximum: 2.6 mmol/L). Fourteen (30.4%) patients had severe hypocalcemia (<1.8 mmol/L) and required parenteral correction. A comparison between hypocalcemia and patients with normal calcium indicated that the significant predictor of hypocalcemia was pretreatment parathyroid hormone levels (9.9 ± 11.8vs 7.6 ± 2.56 pmol/L, respectively; P < .005). The prognostic role of parathyroid hormone for the denosumab-associated hypocalcemia was assessed using ROC curve analysis. For the cut-off value of Parathyroid hormone = 6.8 pmol/L, giving serum parathyroid measurement an AUC of 0.668 (0.599-0.737) - P = .0007; sensitivity 85%; specificity 52%. Conclusion: Hypocalcemia induced by the denosumab treatment is more prevalent than previously shown in patients with osteoporosis receiving adequate calcium and vitamin D supplements. An elevated parathyroid hormone predicts hypocalcemia related to denosumab therapy in patients with normal calcium and vitamin D levels.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.

BACKGROUND/AIMS: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. METHODS: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. RESULTS: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. CONCLUSION: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

The role of bone modifying agents for secondary osteoporosis prevention and pain control in post-menopausal osteopenic breast cancer patients undergoing adjuvant aromatase inhibitors.

Introduction: Hormonal therapy (HT) blocks the hormone-mediated growth signal dramatically reducing estrogenic levels with aromatase inhibitors (AIs) becoming a crucial component of the treatment mainstay in patients with early breast cancer (BC). Postmenopausal BC patients receiving HT present with a significant risk of secondary osteoporosis with AIs further reducing estrogen levels and ultimately leading to an accelerated rate of bone resorption and thus decreased bone mineral density (BMD). This was an observational retrospective clinical study that consecutively enrolled early BC patients with osteopenia to compare the impact of alendronate versus denosumab on secondary osteoporosis prevention and pain control. Methods: We identified two groups of patients treated with denosumab 60 mg by subcutaneous injection once every six months or alendronate 70 mg orally once a week. All the patients underwent a baseline physiatric evaluation (T0) and underwent a follow-up visit after 18 months (T1) together with femoral and vertebral Dual-Energy X-ray Absorptiometry (DEXA) exam evaluating T-Score marks. From September 2015 to December 2019 a total of 50 early (stage I-III) BC patients were considered eligible and consecutively enrolled in our study if they met pre-specified inclusion criteria. Results: In the entire observed population, the addition of treatment with alendronate or denosumab led to a significant T-score improvement at the lumbar spine level (-1.92 vs -1.52, p=0.03), with a comparable contribution from alendronate (-1.60 vs -1.45, p=0.07) and denosumab (-2.26 vs -1.58, p=0.07). Regarding the femoral region, neither alendronate (-0.98 vs -1.07, p=0.23) nor denosumab (-1.39 vs -1.34, p=0.81) were able to produce any statistically relevant effect. However, concerning pain control, BMAs had a significant impact on reducing NRS scoresin the general population (T1 3.94 vs. baseline 4.32, p=0.007), with a likelyspecific contribution from alendronate (T1 3.52 vs. baseline 3.88, p=0.004) compared to denosumab (T1 4.36 vs baseline 4.76, p=0.12), without any differences in analgesic therapy assumption over time (p=0.93). Discussion: Both alendronate and denosumab significantly contributed to preventing secondary osteoporosis in early BC patients with low BMD undergoing AIs, mostly at the lumbar spine level. Moreover, alendronate seemed to significantly impact pain control in such patients further supporting alendronate as a cost-effective option in this frail setting, although BMAs particularities should be carefully considered on an individual basis according to specific clinical contexts.

Effect of Denosumab on Bone Density in Postmenopausal Osteoporosis: A Comparison with and without Calcium Supplementation in Patients on Standard Diets in Korea.

The side effects and safety issues tied to calcium supplementation raise questions about its necessity in osteoporosis treatment. We retrospectively evaluated 189 postmenopausal osteoporosis patients treated with denosumab for 12 months. Patients exhibited neither renal dysfunction nor compromised general dietary intake. Patients were divided into three groups as follows: group A, weekly vitamin D 7000 IU; group B, daily vitamin D 1000 IU with elemental calcium 100 mg; and group C, daily vitamin D 1000 IU with elemental calcium 500 mg. All groups showed significant increases in bone density: +6.4 ± 4.7% for the lumbar spine, +2.2 ± 3.5% for the femoral neck, and +2.4 ± 3.8% for the total hip in group A; +7.0 ± 10.9% for the lumbar spine, +2.3 ± 5.2% for the femoral neck, and +2.4 ± 3.8% for the total hip in group B; and + 6.7 ± 8.7% for the lumbar spine, +2.5 ± 8.4% for the femoral neck, and +2.3 ± 4.0% for the total hip in group C. Serum calcium levels increased over time in all three groups with no significant difference. Changes in CTX and P1NP levels did not differ between the groups (all p > 0.05). With regular dietary intake, calcium supplementation levels showed no significant effect on bone density, bone marker changes, or hypocalcemia incidence during denosumab treatment.

Severe hypocalcemia after denosumab treatment leading to refractory ventricular tachycardia and veno-arterial extracorporeal membrane oxygenation support: a case report.

BACKGROUND: Severe hypocalcemia may lead to life-threatening arrhythmias. Denosumab is an effective treatment for osteoporosis that allows long intervals between doses. However, there is a risk of hypocalcemia in some patients. Due to the long half-life of denosumab, emergency physicians caring for patients presenting with symptoms of hypocalcemia may not be aware of the medication, and adverse effects may last longer. CASE PRESENTATION: A 55-year-old woman with a history of systemic lupus erythematosus (SLE) and anxiety disorder called for an ambulance for symptoms of hyperventilation and muscle cramps. After evaluation at the local hospital, she developed pulseless ventricular tachycardia and was resuscitated by defibrillation by the hospital staff. After conversion to sinus rhythm, she was transported to a tertiary center. Upon arrival, pulseless ventricular tachycardia occurred again, and veno-arterial extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pumping (IABP) were implemented. Laboratory results showed severe hypocalcemia (corrected calcium level of 5.3 mg/dL) whereupon intravenous calcium supplementation was started. She had received the first dose of denosumab (60 mg) by subcutaneous injection 24 days prior to hospitalization. She was eventually weaned from ECMO and IABP support. CONCLUSION: Cardiac arrest due to hypocalcemia is relatively rare but can be fatal. In the present case, hyperventilation may have acutely exacerbated pre-existing hypocalcemia, leading to ventricular tachycardia. The patient had a slightly decreased serum calcium level prior to denosumab. Close monitoring may be preferable after the primary dose of denosumab in selected patients. Emergency physicians caring for patients who may be suffering from symptoms/signs of hypocalcemia must be mindful of medications that have long half-lives and affect electrolyte balance when treating fatal arrhythmia due to hypocalcemia.

Vitamin D Toxicity Masquerading as Acute Pancreatitis.

Patients and medical professionals are showing renewed interest in vitamin D supplementation as a result of increased knowledge of the positive health effects of vitamin D supplementation, the prevalence of vitamin D deficiency, and the easy availability of over-the-counter vitamin D pills. We present a case of acute pancreatitis following vitamin D toxicity due to the administration of doses exceeding the recommended dosage. A 61-year-old man presented to us with elevated pancreatic enzymes, increased 25-hydroxyvitamin D (25-OHD) levels, and deranged renal function tests. He was kept nil per oral and managed with intravenous fluids and denosumab injection. We advocate educating medical professionals about the frequently disregarded side effect of vitamin D supplementation. At the same time, it is critical to create awareness among the public about the harmful effects of self-medication.

Cardiovascular benefits and risks associated with calcium, vitamin D, and antiresorptive therapy in the management of skeletal fragility.

Osteoporosis affects one in every five women over the age of 50 worldwide. With a rapidly ageing population, the prevalence of fragility fractures, considered a largely preventable consequence of osteoporosis, is expected to increase. Age is also a major risk for cardiovascular disease and mortality, thus highlighting the importance of cardiovascular profiling of osteoporosis interventions. Although calcium and vitamin D are essential for a healthy bone metabolism, excessive supplementation may be associated with increased risk. Conversely, early pre-clinical data have suggested a possible cardiovascular benefit from bisphosphonate therapy. This review evaluates the evidence behind the cardiovascular benefits and risks that may be associated with osteoporosis therapy.

Bone health in breast cancer.

Early breast cancer is among the most common cancers worldwide. Recent advances continue to improve outcomes and increase long-term survivorship. However, therapeutic modalities are deleterious for patients' bone health. While antiresorptive therapy may partially negate this, consequent reduction in rates of fragility fractures remains unproven. Selective prescription of bisphosphonates or denosumab may be an amicable middle ground. Recent evidence also suggests a possible role of osteoclast inhibitors as adjuvant therapy, but the evidence is modest at best. In this narrative clinical review, we explore the impact of various adjuvant modalities on bone mineral density and fragility fracture rates of early breast cancer survivors. We also review optimal patient selection for antiresorptive agents, their impact on rates of fragility fractures, and the possible role of these agents as adjuvant therapy.

Denosumab-induced hypocalcemia post bariatric surgery-a severe and protracted course: a case report.

BACKGROUND: Denosumab is known to cause abnormalities in calcium homeostasis. Most of such cases have been described in patients with underlying chronic kidney disease or severe vitamin D deficiency. Previous bariatric surgery could also contribute to hypocalcemia and deterioration in bone health. CASE PRESENTATION: We present a case of a 61-year-old Malay female with worsening bilateral limb weakness, paresthesia, and severe carpopedal spasm a week after receiving subcutaneous denosumab for osteoporosis. She had a history of gastric bypass surgery 20 years ago. Post gastric bypass surgery, she was advised and initiated on lifelong calcium, vitamin D, and iron supplementations that she unfortunately stopped taking 5 years after surgery. Her last serum blood tests, prior to initiation on denosumab, were conducted in a different center, and she was told that she had a low calcium level; hence, she was advised to restart her vitamin and mineral supplements. Laboratory workup revealed severe hypocalcemia (adjusted serum calcium of 1.33 mmol/L) and mild hypophosphatemia (0.65 mmol/L), with normal magnesium and renal function. Electrocardiogram showed a prolonged QTc interval. She required four bolus courses of intravenous calcium gluconate, and three courses of continuous infusions due to retractable severe hypocalcemia (total of 29 vials of 10 mL of 10% calcium gluconate intravenously). In view of her low vitamin D level of 33 nmol/L, she was initiated on a loading dose of cholecalciferol of 50,000 IU per week for 8 weeks. However, despite a loading dose of cholecalciferol, multiple bolus courses, and infusions of calcium gluconate, her serum calcium hovered around only 1.8 mmol/L. After 8 days of continuous intravenous infusions of calcium gluconate, high doses of calcitriol 1.5 µg twice daily, and 1 g calcium carbonate three times daily, her serum calcium stabilized at approximately 2.0 mmol/L. She remained on these high doses for over 2 months, before they were gradually titrated down to ensure sustainability of a safe calcium level. CONCLUSION: This case report highlights the importance of screening for risk factors for iatrogenic hypocalcemia and ensuring normal levels before initiating denosumab. The patient history of bariatric surgery could have worsened the hypocalcemia, resulting in a more severe presentation and protracted response to oral calcium and vitamin D supplementation.

Monoclonal antibodies for treatment of osteoporosis.

Osteoporosis is a chronic disease with high unmet medical need. It is characterized by low bone mass and deteriorated bone architecture, leading to increased risk of fragility fractures, with vertebral and hip fractures representing the highest risk of morbidity and mortality. The baseline therapeutic approach to osteoporosis treatment has been based on adequate intake of calcium and supplementation of vitamin D. In this review, we focus on two approved monoclonal antibodies, romosozumab and denosumab, which have been shown to be efficient and safe options to prevent patient fractures. Romosozumab is a humanized monoclonal antibody IgG2 isotype that extracellularly binds sclerostin with high affinity and specificity. Denosumab is a fully human monoclonal antibody IgG2 isotype that binds RANK ligand (RANKL) and prevents the interaction of RANKL with its receptor RANK. Denosumab is an antiresorptive that has been used for more than a decade, and romosozumab has recently been approved for clinical practice worldwide.

Review of bone health in women with estrogen receptor-positive breast cancer receiving endocrine therapy.

In estrogen-receptor-positive tumors, adjuvant endocrine therapy has been shown to be highly beneficial for both overall and disease-free survival. Estradiol is key in regulating bone and mineral physiology, and several studies found a strong correlation between these therapies and the risk of fractures. Since these therapies are often given for 5 through 10 years, the timing for bisphosphonates or denosumab initiation seems essential to managing bone metabolism. However, gray zones and discrepancies between guidelines remain as to the best threshold when to start antiresorptive treatment, or whether antiresorptive treatment should be administered to every woman undergoing adjuvant endocrine therapy, independent of their risk factors for fractures. Treatment options and strategies should be discussed at the start of hormone adjuvant therapy to come to a shared decision with the patient, with the final aim of reducing the risk of future fractures as much as possible. This review will cover present guidelines and literature on antiresorptive treatment in this setting, to provide clinicians with useful clues for managing these patients.

The clinical effectiveness of denosumab (Prolia®) in patients with hormone-sensitive cancer receiving endocrine therapy, compared to bisphosphonates, selective estrogen receptor modulators (SERM), and placebo: a systematic review and network meta-analysis.

This systematic review (SR) assessed the use of denosumab (Prolia®) to treat osteoporosis in cancer patients receiving endocrine therapy. Denosumab was found to prevent vertebral fractures and improve bone mineral density in cancer patients with osteoporosis. This is the first SR to assess treating osteoporotic cancer patients with denosumab. PURPOSE: This study assessed the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs) (bazedoxifene, raloxifene) and placebo for the treatment of osteoporosis in hormone-sensitive cancer patients receiving endocrine therapy (men with prostate cancer [MPC] on hormone ablation therapy [HAT], and women with breast cancer [WBC] on adjuvant aromatase inhibitor therapy [AAIT]). METHODS: Systematic literature searches were conducted in three biomedical databases to identify randomized controlled trials (RCTs). Frequentist network meta-analyses and/or pairwise meta-analyses were performed on predetermined outcomes (i.e., vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, treatment-related adverse events [AEs], serious AEs [SAEs], withdrawal due to treatment-related AEs). RESULTS: A total of 14 RCTs (15 publications) were included. Denosumab was found to prevent vertebral fractures in cancer patients receiving endocrine therapy, relative to placebo. Similarly, denosumab, zoledronate, and alendronate improved BMD at the femoral neck (FN) and lumbar spine (LS) in MPC on HAT, relative to placebo. Denosumab, ibandronate and risedronate improved BMD at the LS and total hip (TH) in WBC on AAIT, relative to placebo. Denosumab and risedronate improved trochanteric (TRO) BMD in WBC on AAIT, relative to placebo. Similarly, denosumab improved FN BMD in WBC on AAIT. CONCLUSION: In MPC on HAT, denosumab (relative to placebo) was effective at preventing vertebral fractures and improving BMD at the FN and LS. Moreover, in WBC on AAIT, denosumab (relative to placebo) improved BMD at the FN, LS, TH, and TRO, as well as prevent vertebral fracture.

Managing Bone Health in Breast Cancer.

OBJECTIVE: Osteoporosis is a common condition that can be caused or exacerbated by estrogen deficiency. METHODS: This narrative review will discuss optimizing bone health in the setting of adjuvant endocrine treatments for hormone receptor-positive breast cancer and the current use of antiresorptive agents as adjuvant therapy and as bone modifying agents. RESULTS: Adjuvant endocrine treatments for hormone receptor-positive breast cancer (tamoxifen and aromatase inhibitors) affect bone health. The exact effect depends on the agent used and the menopausal state of the woman. Antiresorptive medications for osteoporosis, bisphosphonates and denosumab, lower the risk of bone loss from aromatase inhibitors. Use of bisphosphonates as adjuvant treatment in breast cancer, regardless of hormone receptor status, is increasing because of benefits seen to cancer relapse and survival. CONCLUSION: Optimizing bone health in women with breast cancer during and after cancer treatment is informed by an understanding of breast cancer treatment and its skeletal effect.

Novel Treatment Options in Childhood Bone Diseases.

BACKGROUND: Several novel treatment options have recently become available in childhood bone diseases. The purpose of this article is to provide an update on some of the therapeutic agents used in the treatment of pediatric osteoporosis, X-linked hypophosphatemic rickets, and achondroplasia (ACH). SUMMARY: Vitamin D3 and Ca supplementation remains the basis of childhood osteoporosis treatment. Bisphosphonate (BP) therapy is the main antiresorptive therapeutic option, while denosumab, a human monoclonal IgG2 antibody with high affinity and specificity for a primary regulator of bone resorption - RANKL, represents a possible alternative. Its potent inhibition of bone resorption and turnover process leads to continuous increase of bone mineral density throughout the treatment also in the pediatric population. With a half-life much shorter than BPs, its effects are rapidly reversible upon discontinuation. Safety and dosing concerns in children remain. Novel treatment options have recently become available in two rare bone diseases. Burosumab, a monoclonal antibody against FGF-23, has been approved for the treatment of children with X-linked hypophosphatemic rickets older than 1 year. It presents an effective, more etiology-based treatment for rickets compared to conventional therapy, without the need for multiple daily oral phosphate supplementation. Its long-term efficacy and safety are currently being investigated. After years of anticipation, a novel treatment option for ACH has become available. C-type natriuretic peptide analog vosoritide effectively increases proportional growth and has a reasonable safety profile in children >2 years. Its effect on other features of the disease and the final height is yet to be determined. Several other treatment options for ACH exploring different therapeutic approaches are currently being investigated. KEY MESSAGES: Denosumab is effective in the treatment of childhood-onset osteoporosis; however, further studies are necessary to determine the optimal treatment protocol. Burosumab is more etiology-based and convenient in comparison to conventional treatment of X-linked hypophospha--temic rickets in children and adults. Vosoritide importantly changes the natural course of achondroplasia, at least in the short term.

Evaluation of denosumab in adult oncology patients for the prevention of skeletal related events across a large academic health system.

INTRODUCTION: Denosumab (Xgeva®) and zoledronic acid (Zometa®) are widely utilized for prevention of skeletal related events (SREs) in oncology patients. Drug costs, renal function, ease and logistics of administration, and adverse effect profile are factors frequently considered by patients and/or providers when selecting an optimal agent. Given the significantly higher drug cost of denosumab compared to zoledronic acid, an evaluation of our institution's denosumab use and investigation into opportunities to shift denosumab administrations to zoledronic acid and/or to lower cost sites-of-care was warranted. METHODS: A single-center, multi-site, retrospective, observational analysis of the electronic medical record (EMR) was conducted for adult oncology patients who received denosumab 120 mg for prevention of SREs from October 1st, 2018 to September 30th, 2019 at three institutions within our health system. Additional information was collected to characterize the patient population based on cancer diagnosis, renal function, and concomitant calcium and vitamin D supplementation. Our primary objective was to evaluate if the use of denosumab met current formulary restrictions of the health system. RESULTS: In total, 304 adult oncology patients received 1411 doses of denosumab for the prevention of SREs. The majority of reviewed patients had a primary oncology diagnosis of breast (35%) or lung (24%) cancer. Of the patients who received denosumab, 278 (93%) met the health system's current formulary restrictions. The majority of patients who did not meet formulary restrictions were those with multiple myeloma (MM) (20/22; 91%). Of the 304 patients reviewed, 70 had the appropriate parameters in the EMR to calculate creatinine clearance (CrCl) using Cockcroft-Gault Equation. Of those 70 patients, 59 (84%) would have been eligible to receive zoledronic acid instead of denosumab given that their CrCl >30 mL/min with no documented intolerance to bisphosphonates. Concurrent use of calcium and vitamin D is recommended when using denosumab. Based on the most recent prior to admission (PTA) medication list obtained from the 304 patients evaluated, 222 (73%) had both calcium and vitamin D listed as "taking". CONCLUSIONS: Within our health system, denosumab is restricted to those who meet formulary restrictions. Additional education is recommended to help limit the use of denosumab, specifically in MM, to reduce drug costs when zoledronic acid is also an appropriate first-line agent.