Osteoporosis

Dr. Janet Schlechte May, 2019

Dr. Chermaine Hung, PGY-2

Mentor: Dr. Shibli-Rahhal

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Definition Bone Mineral Density Measurement (BMD) BMD T-score at hip and spine

Osteopenia BMD 1-2.5 SD below mean for young adult women T Score -1 to -2.5

Osteoporosis BMD -2.5 SD below normal mean for young adult women T score < -2.5

Severe osteoporosis BMD -2.5 SD below normal mean for young adult women in a patient who had at least 1 fracture T Score < -2.5

Risk Prediction

* Obtain Dual-energy X-ray absorptiometry (DXA) scan.

o If osteoporosis then treatment is recommended.

o If osteopenia, use Fracture Risk Assessment Tool (FRAX) to evaluate risk. https://www.sheffield.ac.uk/FRAX/tool.aspx?country=9

* Treatment recommended if:

o Prior hip or spine fracture

o BMD T-score <-2.5 at hip or spine

o Osteopenia and 10-year hip fracture risk > 3%

o Osteopenia and 10-year risk of major osteoporotic fracture > 20%

Treatments

* Bisphosphonates

o Bind to bone mineral matrix and inhibit osteoclast-driven bone resorption. Use associated with decreased fracture at multiple sites.

o Available in intravenous or oral forms.

o Side effects: gastrointestinal upset, osteonecrosis of the jaw (ONJ), subtrochanteric femur fractures.

o Concern about clearance in chronic kidney disease, may be safe in CKD3

* Denosumab

o RANK ligand inhibitor. Prevents osteoclast precursors from maturing, decreasing bone resorption.

o Subcutaneous injection every 6 months.

o Side effects: ONJ, subtrochanteric fracture, rapid bone loss after stopping

o Can be used in kidney disease

* Parathyroid hormone and PTH-rp analogues (teriparatide, abaloparatide in US)

o Stimulate bone formation. Subcutaneous injection daily.

o Contraindicated in hyperparathyroidism, conditions associated with bone cancer

* Romosozumab

o Monoclonal antibody that inhibits sclerostin (normally secreted by osteocytes to decrease bone formation and stimulate bone resorption).

o Dual action drug.

o Monthly subcutaneous injection.

* Hormone replacement therapy

o Estrogen: use only in a young patient with low risk of breast cancer.

o Selective estrogen receptor modulators: decreases bone resorption

o Both associated with increased risk of stroke, DVT

References

1. Aghaloo T, Hazboun R, Tetradis S. Pathophysiology of Osteonecrosis of the Jaws. Oral Maxillofac Surg Clin North Am. 2015 Nov;27(4):489-96. doi: 10.1016/j.coms.2015.06.001. Epub 2015 Sep 26. PMID: 26412796

2. Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwiński E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster JY, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. 2017 Jul;5(7):513-523. doi: 10.1016/S2213-8587(17)30138-9. Epub 2017 May 22. PMID: 28546097.

3. Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. 2019 Jan 26;393(10169):364-376. doi: 10.1016/S0140-6736(18)32112-3. PMID: 30696576.

4. Desai RJ, Mahesri M, Abdia Y, et al. Association of Osteoporosis Medication Use After Hip Fracture With Prevention of Subsequent Nonvertebral Fractures: An Instrumental Variable Analysis. JAMA Netw Open. 2018;1(3):e180826.

5. Festuccia F, Jafari MT, Moioli A, Fofi C, Barberi S, Amendola S, Sciacchitano S, Punzo G, Menè P. Safety and efficacy of denosumab in osteoporotic hemodialysed patients. J Nephrol. 2017 Apr;30(2):271-279. doi: 10.1007/s40620-016-0334-1. Epub 2016 Jul 9.

6. Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc. 2009 Jul;84(7):632-7; quiz 638. doi: 10.1016/S0025-6196(11)60752-0. PMID: 19567717; PMCID: PMC2704135.

7. Lewiecki EM, Bilezikian JP. Denosumab for the treatment of osteoporosis and cancer-related conditions. Clin Pharmacol Ther. 2012 Jan;91(1):123-33. doi: 10.1038/clpt.2011.268. Epub 2011 Dec 7. PMID: 22158568.

8. Lewiecki EM. Role of sclerostin in bone and cartilage and its potential as a therapeutic target in bone diseases. Ther Adv Musculoskelet Dis. 2014 Apr;6(2):48-57. doi: 10.1177/1759720X13510479. PMID: 24688605; PMCID: PMC3956136.

9. Pouresmaeili F, Kamalidehghan B, Kamarehei M, Goh YM. A comprehensive overview on osteoporosis and its risk factors. Ther Clin Risk Manag. 2018;14:2029-2049. Published 2018 Nov 6. doi:10.2147/TCRM.S138000

10. Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005 Dec;115(12):3318-25. doi: 10.1172/JCI27071. PMID: 16322775

11. Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11. PMID: 28892457.

12. Tu KN, Lie JD, Wan CKV, et al. Osteoporosis: A Review of Treatment Options. P T. 2018;43(2):92-104.

13. U.S. Preventive Services Task Force: Osteoporosis to prevent fractures: screening (2018). U.S. Preventive Services Task Force (USPSTF). Rockville, MD: U.S. Dept. of Health & Human Services, Agency for Healthcare Research and Quality.

14. World Health Organization (WHO). WHO scientific group on the assessment of osteoporosis at primary health care level: summary meeting report. Available at: https://www.who.int/chp/topics/Osteoporosis.pdf.

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