Introduction: Severe hypercalcemia is most commonly caused by primary hyperparathyroidism (PHPT) and malignancy. While standard therapies are effective in most cases, a subset of patients have persistent or refractory hypercalcemia. We present a retrospective case series detailing the clinical characteristics, biochemistry, and outcomes of patients treated with denosumab for hypercalcemia. Cases: Seven patients with severe hypercalcemia were identified, comprising five with PHPT and two with malignancyassociated hypercalcemia. The mean age was 70.4 years (range 55–86), with 71% female (n = 5) and 29% male (n = 2). Baseline corrected calcium ranged from 2.92 to 4.59 mmol/L, with a mean of 3.26 mmol/L. In the PHPT cohort, parathyroid hormone (PTH) levels were significantly elevated (16.7–168 pmol/L), while malignancy patients had suppressed PTH (0.6 and 0.9 pmol/L). Prior to denosumab, 4/7 patients (57%) received bisphosphonates, 3/7 (43%) received calcitonin, and 1/7 (14%) was treated with cinacalcet. Denosumab resulted in a mean reduction in corrected calcium of 0.22 mmol/L from 3.26 to 3.03 mmol/L. Biochemical response was observed in 5/7 patients (71%). Of these, 3 patients (43%) achieved normocalcemia, while 2 patients (29%) demonstrated a partial response. The remaining 2/7 patients (29%) showed no significant improvement in calcium levels. Among responders, the mean time to calcium reduction to <3.0 mmol/L was 27 days (range 7–47). Repeat dosing was required in the majority of patients, with a mean of 1.7 doses per patient (range 1–4), indicating variability in both onset and durability of response. Among patients with PHPT, four underwent parathyroidectomy, and one declined surgery. Both patients with malignancy were managed nonsurgically. Conclusion Denosumab achieved normocalcemia in 43% of patients, with additional partial responses. Its effects were variable, with delayed response and frequent need for repeat dosing, supporting its role as an adjunctive or bridging therapy rather than as a definitive treatment.
Denosumab ; Hypercalcemia ; Retrospective Studies

Introduction: Severe hypercalcemia is a life-threatening metabolic emergency that necessitates prompt initiation of systemic therapy due to the risk of cardiac arrhythmias. It is frequently linked to squamous cell carcinoma through the production of parathyroid hormone–related protein, which mediates the development of humoral hypercalcemia of malignancy. Case: This is a case of a 38-year-old male who was diagnosed 1 year ago with locally advanced poorly differentiated basaloid squamous cell carcinoma of the lower anterior mandibular alveolus involving cortical, medullary bone, and perineural invasion. He underwent extensive tumor resection with reconstruction, tracheostomy, and bilateral neck dissection, followed by multiple revision surgeries for postoperative complications. He completed adjuvant chemoradiotherapy. He presented with acute confusion without other systemic symptoms. His Glasgow Coma Scale was E4V4M5. Neurological and systemic examinations were unremarkable, and oral cavity assessment showed no evidence of recurrence. Investigations revealed severe hypercalcemia (5.94 mmol/L) with normal phosphate (1.16 mmol/L) associated with shortened QTc. Other tests were unremarkable, with no evidence of infection, uremia, liver dysfunction, or alternative metabolic causes. Lumbar puncture was unremarkable. His parathyroid hormone level was suppressed at 0.50 pg/ mL. Computed tomography brain showed no evidence of meningoencephalitis, hydrocephalus, cerebral oedema, or metastasis. Aggressive hydration was initiated alongside subcutaneous calcitonin, which was subsequently titrated. However, there was no clinical or biochemical improvement after 1 day, with persistent confusion and calcium remaining at 5.87 mmol/L. Subcutaneous denosumab was then administered, and hemodialysis was initiated on alternate days due to refractory hypercalcemia. This resulted in improvement of calcium levels to 3.2–3.6 mmol/L and resolution of confusion Conclusion Refractory hypercalcemia may represent a late manifestation of advanced squamous cell carcinoma and is an ominous prognostic indicator, necessitating prompt evaluation and oncologic management.
Calcitonin ; Denosumab ; Hypercalcemia ; Renal Dialysis ; Neoplasms

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

OBJECTIVES: This systematic review examines recent pharmacoeconomic literature on denosumab' cost-effectiveness for bone metastasis treatment, providing evidence-based insights to guide healthcare policy decisions. METHODS: A comprehensive literature search was performed across Cochrane, PubMed, EMBASE (Ovid), CNKI, and Wanfang databases to identify original articles published between 2017 and 2023. Key words consisted of bone metastases, denosumab, and cost-effectiveness in the search strategy. The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022). Data was extracted regarding methodological characteristics and cost-effectiveness analyses. RESULTS: A total of 111 studies were retrieved, of which 6 met the inclusion criteria. All included studies were based on clinical trials and published literature data and exhibited high methodological quality. Up to 83% (5 out of 6) of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid. The adjusted incremental cost-effectiveness ratios varied substantially by tumor type, ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained. CONCLUSIONS The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid. The application of CHEER (2022) enhances the reliability of pharmacoeconomic evaluations.
Denosumab/therapeutic use* ; Humans ; Bone Neoplasms/economics* ; Cost-Benefit Analysis

BACKGROUND AND OBJECTIVES

Giant cell tumor of bone (GCTB) is a benign aggressive tumor primarily treated with surgery. Neoadjuvant treatment with denosumab or zoledronic acid is a common adjunct given to down-stage tumors and facilitate limb sparing surgery. This study sought to determine the characteristics, outcomes, and occurrence of complications following resection (RS) or extended curettage (EC) for GCTB of the lower extremities. Correlation of neoadjuvant therapy with the occurrence of complications was also investigated.

This is an analytical cross-sectional study of 30 patients diagnosed with GCTB of the lower extremity treated between 2015 to 2022 in a single tertiary hospital. Functional outcomes were determined using the 1993 version of the Musculoskeletal Tumor Society (MSTS) score. Mean follow-up for all patients was 2.6 years (SD 1.8). Twenty-two patients (73%) underwent resection, while eight (27%) patients underwent extended curettage. Of the 30 patients, 26 (87%) patients received neoadjuvant therapy, with 21 (81%) given denosumab and five (19%) given zoledronic acid.

Functional outcomes were excellent for 23 patients (77%), with no significant difference between RS and EC groups. Nine complications occurred in the RS group, including dehiscence (n=3), superficial infection (n=2), implant failure (n=1), nonunion (n=1), palsy (n=1), and implant irritation (n=1). Five complications occurred in the EC group, four of which were noted to be recurrences, with one case of deep infection. Recurrence was noted to be significantly higher (p=0.0004) in the EC group. Separate correlation analysis showed no significant difference in incidence of complications but found that duration of surgery was significantly longer (p=0.0001), and intraoperative blood loss was significantly higher (p=0.0072) in the RS group. No significant difference (p=0.78) was noted in complication rate between patients given denosumab versus zoledronic acid.

Functional outcomes of EC and RS appear to be comparable, including the incidence of complications. However, recurrence was noted to be significantly higher in EC. There appears to be no clear advantage between denosumab or zoledronic acid for GCTB. As a neoadjuvant medication and/or to control tumor progression, zoledronic acid may be the more economic option especially for patients in developing countries.

OBJECTIVE: To evaluate the effect of denosumab on bone mineral density around proximal femoral prosthesis after total hip arthroplasty(THA) in the postmenopausal osteoporotic patients. METHODS: Fifty-four consecutive patients underwent unilateral primary THA were included in this retrospective study. Twenty-five patients received denosumab for osteoporosis as the treatment group, and the twenty-nine without denosumab were the control group. At 1 week, 3month, 6 months, and 12 months after THA, bone turnover markers and proximal femoral periprosthetic bone mineral density (BMD) were measured. RESULTS: At 3, 6 and 12 months after operation, the level of TRACP-5b in the control group was significantly higher than that in the treatment group (P<0.05);the level of bone-specific alkaline phosphatase (BALP) between two groups showed significant difference in 12 months after operation (control group was higher than treatment group, P<0.05). The BMD of Gruen 1 and Gruen 7 decreased at 3, 6 and 12 months after operation compared with 1 week after operation. Comparing the treatment group and the control group, the differences of the the decrease of BMD in Gruen 1 and Gruen 7 were no significant at 3 months after surgery. In Gruen 1, Gruen 7 at 6 months after operation and Gruen 1, Gruen 7 at 12 months after operation, the decrease of BMD in the control group was significantly higher than that in the treatment group(P<0.05). It is suggested that desudumab could inhibit the loss of BMD after 6 months, and continuously show a protective effect on bone mass at 12 months after operation. CONCLUSION After THA in postmenopausal patients with osteoporotic femoral neck fracture, Desuzumab can reduce the loss of BMD around the proximal femoral prosthesis and effectively inhibit bone resorption.
Humans ; Arthroplasty, Replacement, Hip ; Bone Density ; Denosumab/therapeutic use* ; Retrospective Studies ; Postmenopause ; Absorptiometry, Photon ; Bone Remodeling ; Follow-Up Studies ; Hip Prosthesis

Osteonecrosis of the jaw (ONJ) is a well-known pathological condition in oncology derived from the use of bisphosphonates (BPs) and denosumab. Many molecular and immunological targets have been introduced for daily use in cancer treatment in recent years; consequently, new cases of ONJ have been reported in association with these drugs, especially if administered with BPs and denosumab. When the drugs are administered alone, ONJ is rarely seen. The objective of our study was to analyze the recent literature relative to the association of ONJ with these new drugs highlighting the pathogenic, clinical and therapeutic aspects. The close collaboration between maxillofacial surgeon, oncologist, dentist, and dental hygienist remains the most important aspect for the prevention, prompt recognition, and treatment of this pathology.
Angiogenesis Modulating Agents ; Cooperative Behavior ; Denosumab ; Dental Hygienists ; Dentists ; Diphosphonates ; Humans ; Immunomodulation ; Immunotherapy ; Jaw ; Oral and Maxillofacial Surgeons ; Oral Manifestations ; Osteonecrosis ; Pathology

Osteoporosis is a skeletal disorder characterized by compromised bone strength resulting in a predisposition to fracture. Osteoporosis-related fractures can lead to pain, disability, and increased healthcare costs. This study aimed to explore different pharmacological treatments for osteoporosis. Various treatments are used to prevent and treat osteoporosis, particularly in postmenopausal women and elderly men, but the approach needs to be individually tailored. Bisphosphonates are most commonly used to treat osteoporosis. Bisphosphonates and denosumab are mainly used during the initial phase of therapy for most patients with osteoporosis, including those with a high risk of fracture. In younger postmenopausal women, menopausal hormone therapy (including tibolone) and selective estrogen receptor modulators may be considered as alternatives for fracture prevention. Parathyroid hormone therapy is recommended for osteoporosis treatment in elderly patients with an increased risk of multiple vertebral fractures. Dual energy X-ray absorptiometry (DXA) is the mainstay for monitoring the treatment response, and clinicians may consider alternative treatments if a significant decrease in bone mineral density is detected (using DXA or bone turnover markers) or if recurrent fractures occur during treatment. For postmenopausal women undergoing long-term bisphosphonate treatment, the risk of fracture should be reassessed after 3 to 5 years, and a “drug holiday” should be considered if the risk of fracture is low-to-moderate. Therapy should be continued for patients who continue to exhibit a high risk of fracture, or alternatively, switching to other treatments may be considered.
Absorptiometry, Photon ; Aged ; Bone Density ; Bone Remodeling ; Denosumab ; Diphosphonates ; Drug Therapy ; Female ; Health Care Costs ; Humans ; Male ; Osteoporosis ; Parathyroid Hormone ; Selective Estrogen Receptor Modulators

BACKGROUND: Giant-cell tumor of bone (GCTB) is a locally aggressive primary benign tumor presenting as an expansile osteolytic lesion affecting the epiphysis of long bones. Denosumab halts the osteolysis by giant cells thereby downstaging the tumor, helping in performing less morbid procedures to remove the tumor. Our aim was to report the incidence of local recurrence (LR) in patients operated following neoadjuvant denosumab, to investigate factors associated with LR following extended curettage for GCTB, and to compare the postoperative functional and oncological outcome of patients operated with and without neoadjuvant denosumab. METHODS: A total of 123 patients with a mean age of 29.6 years undergoing extended curettage for GCTB were retrospectively divided into group 1 receiving neoadjuvant denosumab and group 2 operated without denosumab. The mean follow-up period was 35 months. The perioperative characteristics and outcome were compared between the two groups and the factors for LR of GCTB were analyzed. RESULTS: The incidence of LR among patients operated after neoadjuvant denosumab therapy was 42.8% and was significantly high compared to that in patients without denosumab (p < 0.001). On multivariate logistic regression analysis, use of denosumab as a neoadjuvant was the only factor independently associated with LR following surgery (p = 0.002). Patients treated with denosumab had a lower LR-free survival rate (log-rank, p = 0.018). CONCLUSIONS: Denosumab was independently associated with increased LR following surgery for GCTB. Denosumab has to be used cautiously in patients in whom the burden of downstaging the disease outweighs the possible chance of LR.
Curettage ; Denosumab ; Epiphyses ; Follow-Up Studies ; Giant Cell Tumors ; Giant Cells ; Humans ; Incidence ; Logistic Models ; Osteolysis ; Recurrence ; Retrospective Studies ; Survival Rate

Antiresorptive drugs (ARDs), such as bisphosphonates or denosumab, that prevent bone resorption are widely used in patients with osteoporosis or with cancer that has metastasized to the bones. Although osteonecrosis of the jaw (ONJ) is a well-documented complication of ARD use, the benefits ARDs outweigh the complication. Thus, research has focused on finding ways to prevent or reduce the risk of developing ONJ. Dentists, as part of a multi-professional team, have a critical role in preventing ONJ. However, many dentists tend to hesitate to provide dental care to patients with ONJ, or tend to think that it is a problem to be dealt with by oral surgeons. This review gives an overview of ARD-related ONJ and provides the guidelines for dental care in patients taking ARDs to lower the risk of developing ONJ.
Bone Density Conservation Agents ; Bone Resorption ; Denosumab ; Dental Care ; Dentists ; Diphosphonates ; Humans ; Jaw ; Oral and Maxillofacial Surgeons ; Osteonecrosis ; Osteoporosis