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.

We report two patients with cauda equina syndrome (CES) secondary to L5 giant cell tumour (GCT) who achieved good neurological recovery after treatment with denosumab without surgery. The first patient was a 26-year-old man with L5 GCT causing CES who regained bowel and urinary control, muscle power improvement from grade 2 to grade 4 and Oswestry disability index (ODI) improvement from 48 to 23 after denosumab treatment. The second patient was a 25-year-old woman with L5 GCT causing CES who regained bowel and urinary control, muscle power improvement from grade 0 to grade 4 and ODI improvement from 42 to 20 after denosumab treatment. The usage of denosumab in the treatment of patients with CES due to GCT allows potential neurological recovery without any surgical intervention. If surgery is not contraindicated, more time is obtained to prepare the patient preoperatively to attain safer surgery and to achieve complete tumour clearance.
Adult ; Cauda Equina* ; Denosumab* ; Female ; Giant Cells* ; Humans ; Polyradiculopathy* ; Spine*

Denosumab, a specific inhibitor of RANK ligand, is a novel therapy for postmenopausal osteoporosis and related disorders. An extensive clinical development program has evaluated the clinical efficacy and safety of denosumab with several thousand patients being followed for up to 10 years. Combined with more than six years of postmarketing experience, these studies provide substantial confidence that denosumab is a convenient and appropriate treatment for patients, including Asians, at high risk for fracture. This review will summarize the clinical development of denosumab and lessons learned since its approval for clinical use in 2010.
Asian Continental Ancestry Group ; Denosumab* ; Female ; Humans ; Osteoporosis* ; Osteoporosis, Postmenopausal ; RANK Ligand ; Treatment Outcome

Osteoporosis is a common adverse event among patients on glucocorticoid therapy. Glucocorticoids reduce bone formation and increase cortical porosity in proportion to the dose and duration of glucocorticoid use. While the epidemiology of glucocorticoid-induced osteoporosis has been well characterized, its pathophysiology and effective management remain unclear. Several recommendations for glucocorticoid-induced osteoporosis are used to determine which patients on long-term glucocorticoid treatment to treat and when. The fracture risk can be assessed using dual-energy X-ray absorptiometry and the Fracture Risk Assessment Tool algorithm, along with other clinical factors. The management of glucocorticoid-induced osteoporosis includes anti-osteoporotic therapy and measures to prevent bone loss. Bisphosphonates are currently the first choice treatment, with teriparatide and denosumab being alternatives.
Absorptiometry, Photon ; Bone Density ; Denosumab ; Diphosphonates ; Epidemiology ; Glucocorticoids ; Humans ; Osteogenesis ; Osteoporosis* ; Porosity ; Risk Assessment ; Teriparatide

OBJECTIVES: The aim of this study was to examine the discontinuation and occurrence of fracture during denosumab treatment in Japanese women with primary osteoporosis or rheumatoid arthritis (RA) with osteoporosis. METHODS: This retrospective study included 143 patients with primary osteoporosis and 96 patients with RA and osteoporosis who were treated with denosumab. Treatment discontinuation, fracture occurrence, lumbar spine (L1–4) bone mineral density (LS-BMD), and bilateral total hip BMD (TH-BMD) were examined before and at 1 and 2 years after treatment commencement. RESULTS: In the primary osteoporosis group, 32 cases dropped out and no fractures occurred from 0 to 1 year. Eighteen cases were lost to follow-up and no fractures were noted from 1 to 2 years. In the RA with osteoporosis group, 7 cases dropped out and no fracture occurred from 0 to 1 year. Twenty-one cases were lost to follow-up and 2 nonvertebral fractures were noted from 1 to 2 years. In this group, 13 cases dropped out from 1 to 2 years and 16 cases dropped out during the 2-year study period due to economic reasons. LS-BMD and TH-BMD values increased continuously for 2 years of treatment in both primary osteoporosis and RA with osteoporosis groups. CONCLUSIONS: These results suggest that during denosumab therapy, the discontinuation rate is expected to remain low during 2 years of treatment in primary osteoporotic patients. In RA patients with osteoporosis, however, the discontinuation rate may increase due to economic reasons from 1 to 2 years of therapy.
Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; Bone Density ; Compliance* ; Denosumab* ; Female ; Hip ; Humans ; Lost to Follow-Up ; Osteoporosis* ; Retrospective Studies ; Spine

Osteoporosis is a common senile disease that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. Currently, good anti-fracture data supports many available anti-resorptive and anabolic drugs including bisphosphonates, selective estrogen receptor modulators, and recombinant human parathyroid hormones. Calcium and vitamin D are also essential treatments for the prevention and treatment of osteoporosis. Although, bisphosphonate is the cornerstone of osteoporosis treatment and is considered as the first line of therapy, their duration of therapy and long-term safety is under question. Novel agents, particularly denosumab, inhibitors of cathepsin K, andanabolic agents that act on Wnt signaling, will increase the therapeutic options for clinicians in the coming years.
Antibodies, Monoclonal, Humanized ; Calcium ; Cathepsin K ; Diphosphonates ; Female ; Humans ; Osteoporosis ; Osteoporosis, Postmenopausal ; Selective Estrogen Receptor Modulators ; Vitamin D ; Denosumab

Denosumab, a fully human recombinant monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL), blocks binding of RANKL to the RANK receptor, found on the surface of osteoclasts and osteoclast precursors, resulting in decreased bone resorption. Subcutaneous denosumab administration once every 6 months increases bone mineral density at the lumbar spine, total hip, and/or femoral neck, and reduces markers of bone turnover significantly in postmenopausal women with osteoporosis. Relative to placebo, denosumab treatment reduces the risk of vertebral, nonvertebral, and hip fractures significantly. The benefits of denosumab treatment are generally obvious after the first dose and were continued for up to 8 years of treatment in an extension study. The tolerability profile of denosumab during this extension phase was consistent with that observed during the initial 3-year FREEDOM trial. Postmarketing safety surveillance has not shown any unexpected findings. Ongoing safety surveillance will more fully define the long-term safety of denosumab. The benefits of denosumab would seem to be greater than its risks. Denosumab is an important choice in the treatment of postmenopausal women with osteoporosis at increased risk of fractures, including older patients who have difficulty with oral bisphosphonate intake and patients who are intolerant of, or unresponsive to, other therapies.
Bone Density ; Bone Resorption ; Female ; Femur Neck ; Freedom ; Hip ; Hip Fractures ; Humans ; Osteoclasts ; Osteoporosis* ; RANK Ligand ; Spine ; Denosumab

Osteoporosis is a systemic skeletal disease whose risk increases with age and it is common among postmenopausal women. Currently, almost all pharmacological agents for osteoporosis target the bone resorption component of bone remodeling activity. Current antiresorptive agents are effective, but the effectiveness of some agents is limited by real or perceived intolerance, longterm adverse events (AEs), coexisting comorbidities, and inadequate long-term adherence. New antiresorptive therapies that may expand options for the prevention and treatment of osteoporosis include denosumab, combination of conjugated estrogen/bazedoxifene and cathepsin K inhibitors. However, the long-term efficacy and AEs of these antiresorptive therapies need to be confirmed in studies with a longer follow-up period.
Bone Density Conservation Agents ; Bone Remodeling ; Bone Resorption ; Cathepsin K ; Comorbidity ; Female ; Humans ; Osteoporosis ; Osteoporosis, Postmenopausal* ; Postmenopause ; Denosumab

Despite the rarity of primary bone tumors, osteosarcoma and Ewing sarcoma are the most common primary malignant bone tumors in children and adolescents. Multiagent chemotherapy regimens for neoadjuvant and adjuvant treatment remarkably improved the survival outcome for patients with osteosarcoma and Ewing sarcoma, therefore, most patients are now limb-salvage candidates. However, survival rate reached a plateau for last decades and is still unsatisfactory in the metastatic and relapse setting. Therefore, as seen in denosumab in giant cell tumor, further clinical trials based on molecular mechanism are warranted. This article reviews the current state of the art of systemic chemotherapy by focusing on the clinical heterogeneity of each subtype.
Adolescent ; Child ; Drug Therapy* ; Giant Cell Tumors ; Humans ; Osteosarcoma ; Population Characteristics ; Recurrence ; Sarcoma, Ewing ; Survival Rate ; Denosumab

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