Previous fracture affords the highest risk of future fracture, yet many patients with fragility fractures are not diagnosed as having osteoporosis because of their bone density scores.1
Osteoporosis is underdiagnosed, and because of this, mitigation of fracture risk remains suboptimal.1 Fractures are associated with increased morbidity and mortality, so it is important to identify and treat patients with osteoporosis.2 Diagnosis of osteoporosis is based on a bone mineral density (BMD) test with a T-score of <-2.5.1-3 Treatment is recommended once a diagnosis of osteoporosis has been established.
Treatment should also be considered in a patient with osteopenia and high fracture risk with FRAX 10-year probability of major fracture >20%, or FRAX 10-year probability of hip fracture >3%.1-3
Prior to choosing a treatment modality, it should be determined if there are any secondary causes of osteoporosis.3 If there is no secondary cause of osteoporosis identified, therapy should be chosen carefully based on individual characteristics.
Bisphosphonates are the first-line recommended treatment for most patients with osteoporosis.2-4 They inhibit bone resorption by decreasing osteoclast activity and increasing apoptosis.3 These medications deposit in bone and remain there for prolonged periods of time.3 Bisphosphonates are renally cleared and therefore should be avoided in patients with a creatinine clearance of <35mL/min.5
Side effects of oral bisphosphonates include reflux/esophagitis.3 Intravenous bisphosphonates can cause a short flu-like illness.3 Very rare, but very serious, side effects of bisphosphonates include osteonecrosis of the jaw and atypical subtrochanteric fractures.3 After three to five years of treatment fracture risk should be reassessed, and those with low to moderate risk of fracture can be considered for a “drug holiday.”4
Denosumab is an alternative treatment for osteoporosis.4 Denosumab is an antibody against the receptor activator of nuclear factor NFκβ (RANK) ligand (RANKL), which prevents differentiation, activation and survival of osteoclasts.3 The effects of denosumab are rapidly reversible.2-4 If denosumab is delayed or discontinued and not followed by another therapy, rapid bone loss and increased risk of vertebral fracture occur.2-4
Denosumab is not metabolized or excreted by the kidneys, but patients with moderate to severe chronic kidney disease had higher rates of serious adverse events with this medication.5,6 Denosumab carries similar risk of osteonecrosis of the jaw and atypical hip fractures to bisphosphonates.3 After five to 10 years of treatment fracture risk should be reassessed, and either denosumab should be continued or another osteoporosis therapy should be initiated.4
Parathyroid Hormone (PTH) Analogs
Teriparatide and abaloparatide, administered daily, increase the amount and activity of osteoblasts, improving bone mass.3 These medications are usually reserved for patients with very high fracture risk or previous fragility fractures.3,4
Some contraindications for treatment with PTH analogs include hyperparathyroidism, prior radiation therapy and malignancy.3 In animal studies, long-term PTH analog administration at very high doses has shown increased risk of osteosarcoma, but this has not been observed in humans.3 After completing two years of treatment, antiresorptive therapy should be started to maintain improvements in bone density.3,4
Sclerostin inhibits bone formation, so by inhibiting this, romosozumab acts as an anabolic agent in bone formation.4 Romosozumab can be used in patients who have a very high fracture risk or previous fragility fractures.4
This medication should not be used in patients with increased risk of cardiovascular events or strokes.4 Romosozumab can be used for up to one year and should be followed by antiresorptive therapy to maintain bone density improvements.4
- Siris ES, Adler R, Bilezikian J, et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 2014 May;25(5):1439-43. doi: 10.1007/s00198-014-2655-z. Epub 2014 Feb 28. PMID: 24577348; PMCID: PMC3988515.
- Brown JP. Long-Term Treatment of Postmenopausal Osteoporosis. Endocrinol Metab (Seoul). 2021 Jun;36(3):544-552. doi: 10.3803/EnM.2021.301. Epub 2021 Jun 22. PMID: 34154042; PMCID: PMC8258325.
- Kanis JA, Cooper C, Rizzoli R, Reginster JY. Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2019 Jan;30(1):3-44. doi: 10.1007/s00198-018-4704-5. Epub 2018 Oct 15. Erratum in: Osteoporos Int. 2020 Jan;31(1):209. Erratum in: Osteoporos Int. 2020 Apr;31(4):801. PMID: 30324412; PMCID: PMC7026233.
- Shoback D, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgaa048. doi: 10.1210/clinem/dgaa048. PMID: 32068863.
- Nitta K, Yajima A, Tsuchiya K. Management of Osteoporosis in Chronic Kidney Disease. Intern Med. 2017 Dec 15;56(24):3271-3276. doi: 10.2169/internalmedicine.8618-16. Epub 2017 Oct 11. PMID: 29021477; PMCID: PMC5790712.
- Broadwell A, Chines A, Ebeling PR, et al. Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease. J Clin Endocrinol Metab. 2021 Jan 23;106(2):397-409. doi: 10.1210/clinem/dgaa851. PMID: 33211870; PMCID: PMC7823314.
Dr. Ross received her bachelor’s degree at the University of Alabama, her master’s degree at Georgia State University and her medical degree at Ross University School Medicine. She completed a residency at Wellstar Kennestone Regional Medical Center, a chief residency at University of Illinois/Carle Foundation Hospital and a fellowship at Case Western Reserve University/MetroHealth. Dr. Ross is board-certified by the American Board of Internal Medicine and is a rheumatologist with Wellstar Health System.