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fracture. It has also been proven more effective at boosting BMD than bisphosphonates. Yet in 2018, medical researcher Emma Deeks noted in the journal Drugs & Aging that it remains unclear whether these differences lead to greater anti-fracture efficacy. "Denosumab is a key treatment option for postmenopausal women with osteoporosis who have an increased/high risk of fracture or failure/intolerance of other osteoporosis therapies, although the potential for multiple vertebral fractures to occur after discontinuation of the drug requires consideration of subsequent management options," she concludes. Later studies found denosumab to be an effective treatment for men with osteoporosis, raising BMD in the lumbar spine, neck, hip and one-third radius sites. While other therapies have proven effective in clinical studies, challenges with administering the treatments make them underutilized and other options are needed. EXCITING FINDINGS The status of denosumab as an imperfect solution to age- associated bone loss continues to evolve. One result that has emerged from denosumab studies is the possibility for reduced need for hip revision surgery following total hip arthroplasty. The only available treatment for wear-induced osteolysis after joint replacement surgery to date is revision surgery. This procedure comes with an increased risk of complications and has a higher mortality rate than joint replacement alone. But a proof-of-concept clinical trial by the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, appearing in Lancet Rheumatology in January 2021, found that denosumab can prevent osteolysis and the need for another surgery. "It is very clear from our bone biopsies and bone imaging that the [denosumab] injection stops the bone absorbing the microplastic particles from the replacement joint and therefore could prevent the bone from being eaten away and the need for revision surgery," writes senior author Mark Wilkinson, MBChB, PhD, professor of orthopedics at the University of Sheffield's Department of Oncology and Metabolism, noting that the need for as many as half of all revision surgeries could be eliminated based on this finding. "These results justify the need for future trials that target earlier-stage disease to test for clinical efficacy in reducing the need for revision surgery," the authors conclude. BMD LOSS FROM STEROIDS AND CANCER TREATMENTS Recent research also reveals that denosumab is a promising treatment for bone loss related to certain cancer treatments, which over time can lead to skeletal issues such as osteoporosis, loss of BMD and a high risk for bone fractures. In the journal Expert Opinion on Biological Therapy, November 2020, the authors conclude that denosumab is highly effective at preventing these problems in patients with breast and prostate cancer, as well as nonmetastatic prostate cancer. Denosumab has now outpaced all other therapies, making up 50% of prescriptions by March 2020. Likewise, another recent study found that denosumab offers superior spine BMD increases in patients with bone loss as a result of long-term glucocorticoid treatments. The small study focused on patients receiving long-term prednisolone therapy, revealing that denosumab suppressed bone-turnover markers more effectively than alendronate did after 12 months. The authors have determined that while the results are encouraging, larger randomized controlled trials are necessary. LIMITATIONS AND RISKS While denosumab has been proven effective at increasing BMD and preventing vertebra l fractures, no major difference has been found between denosumab and bisphosphonates in the risk of hip fractures. More research is needed to determine the efficacy of both drugs for this issue. The biggest hurd le the resea rch ha s uncovered during tria ls is the bone loss that occurs after the discontinuation of denosumab, greatly increasing the risk for multiple vertebra l fractures. Some studies found t hat t he rate a nd a mount of bone loss correlates with the leng th of treatment. " The discontinuation of Dmab [denosumab] leads to significant and abrupt changes in bone remodeling," report the authors of a study published in the Journal of Clinical Medicine in January 2021. "Enhanced osteoclastogenesis and osteoblastogenesis is evident at tissue level leading to seriously compromised bone structure." However, preliminary research suggests that bisphosphonates ca n decrea se this bone loss when g iven a f ter denosumab t reat ment ha s stopped . More resea rch is bei n g done to determine the best course of treatment with bisphosphonates and whether administering them prior to starting denosumab a lso decreases bone loss risk. n M D N E W S . C O M /// M D N E W S L O N G I S L A N D ■ 2 0 2 2 2 5

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