Fracture & an Aging World

The history behind the development of romosozumab is fascinating and has to do with a condition known as sclerosteosis, a rare bone dysplasia most common among Dutch Afrikaners in South Africa. Sclerosteosis is caused by six different types of loss-of-function mutations of the SOST gene. In homozygous patients, the condition results in a reduced production of sclerostin and subsequent bony deformities and the impingement of nerves, such as cranial nerves, due to an overgrowth of bones in the skull, ribs, mandible, clavicles, pelvis and long bones. However, heterozygous carriers of these mutations experience increased bone mass in the absence of symptoms. Thus, scientists identified sclerostin as a novel target for drug development and, ultimately, produced romosozumab, which is given as a monthly subcutaneous injection for 12 months.⁸

In 2016, Cosman et al. published the FRAME study, which demonstrated that treatment with romosozumab was associated with a decreased risk of vertebral fracture compared with placebo in postmenopausal women with osteoporosis.⁸ Dr. Saag explained that, when indicated, it’s best to use romosozumab before an antiresorptive agent because doing so yields larger mean bone mineral density increases and greater bone mineral density responder rates than using romosozumab after an antiresorptive medication.⁹

In Sum

Although osteoporosis can be a silent but morbid condition, the lessons imparted by Dr. Saag in his lecture were helpful to an audience eager to aid patients around the globe. Although much work remains to be done for the appropriate screening and treatment of these patients, the future is looking better thanks to the work of many in the field.

Jason Liebowitz, MD, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

References

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2. Nguyen HH, Lakhani A, Shore-Lorenti C, et al. Asian ethnicity is associated with atypical femur fractures in an Australian population study. Bone. 2020 Jun;135:115319.
3. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014 Oct;25(10):2359–2381. Erratum in: Osteoporos Int. 2015 Jul;26(7):2045–2047.
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7. Cummings SR, Ferrari S, Eastell R, et al. Vertebral fractures after discontinuation of denosumab: A post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. 2018 Feb;33(2):190–198.
8. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016 Oct 20;375(16):1532–1543.
9. Cosman F, Kendler DL, Langdahl BL, et al. Romosozumab and antiresorptive treatment: The importance of treatment sequence. Osteoporos Int. 2022 Jun;33(6):1243–1256.