Article

Fragility Fractures: Diagnosis and Treatment

Publish date: December 19, 2018

References

Dietz SO, Hofmann A, Rommens PM. Haemorrhage in fragility fractures of the pelvis. Eur J Trauma Emerg Surg. 2015;41:363-367. doi: 10.1007/s00068-014-0452-1
Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465-475. doi: 10.1359/jbmr.061113.
Gosch M, Hoffmann-Weltin Y, Roth T, Blauth M, Nicholas JA, Kammerlander C. Orthogeriatric co-management improves the outcome of long-term care residents with fragility fractures. Arch Orthop Trauma Surg. 2016; 136(10):1403-1409. doi: 10.1007/s00402-016-2543-4.
Maccagnano G, Notarnicola A, Pesce V, Mudoni S, Tafuri S, Moretti B. The prevalence of fragility fractures in a population of a region of southern Italy affected by thyroid disorders. BioMed Res Int. 2016. doi: 10.1155/2016/6017165.
Mosekilde L, Eriksen EF, Charles P. Effects of thyroid hormones on bone and mineral metabolism. Endocrinol Metab Clin North Am. 1990;19(1):35-63. doi: 10.1016/S0889-8529(18)30338-4.
Liporace FA, Breitbart EA, Yoon RS, Doyle E, Paglia DM, Lin S. The effect of locally delivered recombinant human bone morphogenic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis. J Orthop Traumatol.2015;16(2):151-159. doi: 10.1007/s10195-014-0327-6.
Ilic K, Obradovic N, Vujasinovic-Stupar N. The relationship among hypertension, antihypertensive medications, and osteoporosis: a narrative review. Calcif. Tissue Int. 2013;92(3):217-227. doi: 10.1007/s00223-012-9671-9.
Yesil Y, Ulger, Z, Halil M, et al. Coexistence of osteoporosis (OP) and coronary artery disease (CAD) in the elderly: it is not just a by chance event. Arch Gerontol Geriatr. 2012;54(3):473-476. doi: 10.1016/j.archger.2011.06.007.
Sosa M, Saavedra P, de Tejada MJG, et al, GIUMO Cooperative Group. Beta-blocker use is associated with fragility fractures in postmenopausal women with coronary heart disease. Aging Clin Exp Res.2011;23(3):112-117. doi: 10.3275/7041.
An T, Hao J, Li R, Yang M, Cheng G, Zou M. Efficacy of statins for osteoporosis: a systematic review and met-analysis. Osteoporos Int. 2017;28(1):47-57. doi: 10.1007/s00198-016-3844-8.
Munson JC, Bynum JP, Bell J, et al. Patterns of prescription drug use before and after fragility fracture. JAMA Intern Med. 2016;176(10):1531-1538. doi: 10.1001/jamainternmed.2016.4814.
Saag KG, Agnesdei D, Hans D, et al. Trabecular bone score in patients with chronic glucocorticoid therapy-induced osteoporosis treated with alendronate or teriparatide. Arthritis Rheumatol. 2016;68(9):2122-2128. doi: 10.1002/art.39726.
Chuang MH, Chuang TL, Koo M, Wang YF. Trabecular bone score reflects trabecular microarchitecture deterioration and fragility fracture in female adult patients receiving glucocorticoid therapy: A pre-post controlled study. BioMed Res Int. 2017. doi: 10.1155/2017/4210217.
Andersen BN, Johansen PB, Abrahamsen B. Proton pump inhibitors and osteoporosis. Curr Opin Rheumatol. 2016;28(4):420-425. doi: 10.1097/BOR.0000000000000291.
Jacob L, Hadji P, Kostev K. The use of proton pump inhibitors is positively associated with osteoporosis in postmenopausal women in Germany. Climacteric. 2016; 19(5):478-481. doi: 10.1080/13697137.2016.1200549.
Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fracture. Can Med Assoc J. 2008;179:319-326. doi: 10.1503/cmaj.071330.
Lee RH, Lyles KH, Colon-Emeric C. A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. Am J Geriatr Pharmacother. 2010;8(1):34-46. doi: 10.1016/j.amjopharm.2010.02.003.
Arora E, Singh H, Gupta YK. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention. J Family Med Prim Care. 2016;5(2):248-253. doi: 10.4103/2249-4863.192338.
Maghraoui AE, Roux C. DXA scanning in clinical practice. Q J Med. 2008;101(8):605-617. doi: 10.1093/qjmed/hcn022.
Watts NB, Lewiecki EM, Miller PD, Baim S. National osteoporosis foundation 2008 clinician’s guide to prevention and treatment of osteoporosis and the world health organization fracture risk assessment tool (FRAX): What they mean to the bone densiometrist and bone technologist. J Clin Densitom. 2008;11(4):473-477. doi: 10.1016/j.jocd.2008.04.003.
MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2007;148(3):197-213. doi: 10.7326/0003-4819-148-3-200802050-00198.
Beaton DE, Vidmar M, Pitzul KB, et al. Addition of a fracture risk assessment to a coordinator’s role improved treatment rates within 6 months of screening in a fragility fracture screening program. J Am Geriatr Soc. 2017; 28(3):863-869. doi: 10.1007/s00198-016-3794-1.
U.S. Preventative Services Task Force. Screening for osteoporosis. Ann Intern Med. 2011;154(5):356-364. doi: 10.7326/0003-4819-154-5-201103010-00307.
Sunyecz JA. The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag. 2008;4(4):827-836.
Eastell, R. (1998). Treatment of postmenopausal osteoporosis. N Engl J Med. 1998;338:736-746. doi: 10.1056/NEJM199803123381107.
Cosman F, de Beur SJ, LeBoff MS, et al, National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2381. doi: 10.1007/s00198-014-2794-2.
Black DM, Schartz AV, Ensrud KE, et al, doi:10.1001/jama.296.24.2927.
Schmidt GA, Horner KE, McDanel DL, Ross MB, Moores KG. Risks and benefits of long-term bisphosphonate therapy. Am J Health Syst Pharm. 2010;67(12):994-1001. doi: 10.2146/ajhp090506.
Kraenzlin, ME, Meier C. Parathyroid hormone analogues in the treatment of osteoporosis. Nat Rev Endocrinol. 2011;7(11):647-656. doi: 10.1038/nrendo.2011.108.
Miller P, Hattersley G, Riis B, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis. JAMA. 2016;316(7):722-733. doi: 10.1001/jama.2016.11136.
TYMLOS^TM[prescribing information]. Waltham, MA: Radius Health, Inc; 2017.
Tetsunaga T, Tetsunaga T, Nishida K, et al. Denosumab and alendronate treatment in patients with back pain due to fresh osteoporotic vertebral fractures. J Orthop Sci. 2017;22(2):230-236. doi: 10.1016/j.jos.2016.11.017.
Recker, RR, Mitlak BH, Ni X, Krege JH. Long-term raloxifene for postmenopausal osteoporosis. Curr Med Res Opin. 2011;27(9):1755-1761. doi: 10.1185/03007995.2011.606312.
Yildirim K, Gureser G, Karatay S, et al. Comparison of the effects of alendronate, risedronate and calcitonin treatment in postmenopausal osteoporosis. J Back Musculoskelet Rehabil.2005;18(3/4):85-89. doi: 10.3233/BMR-2005-183-405.
Christensen L, Iqbal S, Macarios D, Badamgarav E, Harley C. Cost of fractures commonly associated with osteoporosis in a managed-care population. J Med Econ. 2010;13(2):302-313. doi: 10.3111/13696998.2010.488969.

TREATMENT

NONPHARMACOLOGIC

Patients with mild osteoporosis may be treated first non-pharmacologically. Lifestyle changes such as calcium and vitamin D supplementation, exercise, and smoking cessation are non-pharmacologic treatment options. Calcium carbonate and calcium citrate are common supplements. Calcium carbonate is 40% elemental calcium, whereas calcium citrate supplements are only 21% elemental calcium. Calcium supplements are best absorbed when taken with food.²⁴ The recommended daily total calcium intake is 1200 mg.²⁵ Only 500 to 600 milligrams of calcium can be absorbed by the GI tract at a time. Therefore, calcium supplements should be taken at least 4 to 5 hours apart.²⁴Patients should also be counseled that calcium supplements may cause GI side effects such as bloating and constipation. To reduce side effects, patients can slowly increase the dose of calcium to a therapeutic level.

Vitamin D supplementation works best in conjunction with calcium supplementation. Vitamin D functions to regulate calcium absorption in the intestine and stimulate bone resorption and maintain the serum calcium concentration. The National Osteoporosis Foundation recommends 800 to 1000 international units of vitamin D daily.²⁴ Lifestyle changes may be sufficient to stop the progression of osteoporosis in its early stages. Once osteoporosis becomes severe enough, pharmacotherapy is needed to stop further bone destruction and improve BMD.

PHARMACOLOGIC

After an initial fragility fracture, the risk of additional ones increases significantly, making treatment of osteoporosis essential. The National Osteoporosis Foundation recommends treating osteoporosis with pharmacotherapy in patients with a high risk of fracture (T score <-2.5) or history of fragility fracture.²⁶ Bisphosphonates inhibit bone resorption and are considered the first-line therapy for postmenopausal women with osteoporosis. A common side effect of oral bisphosphonates is GI toxicity. Patients are advised to avoid lying down for at least 30 minutes after medication administration to avoid esophageal irritation. Oral bisphosphonates should also be taken in the morning on an empty stomach with at least 8 ounces of water. Recurrent bisphosphonate use should be avoided in patients with chronic kidney disease. Oral alendronate and risedronate are typically discontinued after 5 years of use.²⁷ Long-term bisphosphonate use may cause an increased risk of fragility fracture due to oversuppression of bone turnover. To avoid this risk, bisphosphonate “drug holidays” are an option. Bisphosphonates accumulate over time, creating reservoirs. Even after therapy is stopped, patients continue to have therapeutic effects for 2 to 5 years.²⁸

Bisphosphonates are available in both oral and intravenous forms. Alendronate is available in doses of 10 mg and 70 mg for daily and weekly administration, respectively. Both are available in tablet form, but the 70 mg weekly dose is also available in a dissolvable formulation. Alendronate is available in a reduced dose for osteoporosis prevention. Alendronate dosing for osteoporosis prevention is 5 mg daily or 35 mg weekly. Risedronate is dosed as 5 mg daily, 35 mg weekly, or 150 mg monthly. Intravenous bisphosphonates are indicated when oral bisphosphonates are not tolerated, only after vitamin D has been assessed and is within the normal range. Zoledronic acid is administered as a 15-minute infusion once a year.

Teriparatide (Forteo; PTH-1-34) is available for glucocorticoid-induced osteoporosis, postmenopausal women, and men with severe osteoporosis. It is indicated for patients in whom bisphosphonate treatment has failed or those who do not tolerate bisphosphonates. Teriparatide is a synthetic parathyroid hormone (PTH) that acts as an anabolic agent, stimulating bone formation, maturation, and remodeling.²⁹ In addition to its application as a bone-building hormone, teriparatide has gained popularity for various off-label uses. These include accelerated osteosynthesis, stress fracture healing, and in the nonoperative treatment of osteoarthritis.²⁹ Parathyroid hormone has been shown to stimulate the maturation, proliferation, and maintenance of osteoblast progenitor cells. More recently, PTH has been shown to regulate chondrocyte signaling, as well as differentiation and maturation. Further study on the chondroregenerative potential of PTH has demonstrated its efficacy as a novel disease-modifying agent in the treatment of osteoarthritis.²⁹ Teriparatide is administered as a daily subcutaneous injection. The United States dosing is 600 mcg/2.4 mL. Adverse effects such as orthostatic hypotension and osteosarcoma may occur. BMD testing should be performed 1 to 2 years after initiation of teriparatide and every 2 years thereafter.²⁶

Abaloparatide (Tymlos), a human parathyroid hormone, is another treatment option for postmenopausal women at risk of osteoporotic fracture. In a study comparing the efficacy of abaloparatide and teriparatide, treatment with abaloparatide was found to induce higher BMD levels in a time frame of 12 months. The BMD differences could be attributed to many factors, such as an enhanced net anabolic effect or a reduced osteoblast expression. Furthermore, the risk of developing new vertebral and nonvertebral fractures decreased in the abaloparatide group compared with the placebo group over a period of 18 months.³⁰

Continue to: The recommended daily dose for abaloparatide...

References

Dietz SO, Hofmann A, Rommens PM. Haemorrhage in fragility fractures of the pelvis. Eur J Trauma Emerg Surg. 2015;41:363-367. doi: 10.1007/s00068-014-0452-1
Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465-475. doi: 10.1359/jbmr.061113.
Gosch M, Hoffmann-Weltin Y, Roth T, Blauth M, Nicholas JA, Kammerlander C. Orthogeriatric co-management improves the outcome of long-term care residents with fragility fractures. Arch Orthop Trauma Surg. 2016; 136(10):1403-1409. doi: 10.1007/s00402-016-2543-4.
Maccagnano G, Notarnicola A, Pesce V, Mudoni S, Tafuri S, Moretti B. The prevalence of fragility fractures in a population of a region of southern Italy affected by thyroid disorders. BioMed Res Int. 2016. doi: 10.1155/2016/6017165.
Mosekilde L, Eriksen EF, Charles P. Effects of thyroid hormones on bone and mineral metabolism. Endocrinol Metab Clin North Am. 1990;19(1):35-63. doi: 10.1016/S0889-8529(18)30338-4.
Liporace FA, Breitbart EA, Yoon RS, Doyle E, Paglia DM, Lin S. The effect of locally delivered recombinant human bone morphogenic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis. J Orthop Traumatol.2015;16(2):151-159. doi: 10.1007/s10195-014-0327-6.
Ilic K, Obradovic N, Vujasinovic-Stupar N. The relationship among hypertension, antihypertensive medications, and osteoporosis: a narrative review. Calcif. Tissue Int. 2013;92(3):217-227. doi: 10.1007/s00223-012-9671-9.
Yesil Y, Ulger, Z, Halil M, et al. Coexistence of osteoporosis (OP) and coronary artery disease (CAD) in the elderly: it is not just a by chance event. Arch Gerontol Geriatr. 2012;54(3):473-476. doi: 10.1016/j.archger.2011.06.007.
Sosa M, Saavedra P, de Tejada MJG, et al, GIUMO Cooperative Group. Beta-blocker use is associated with fragility fractures in postmenopausal women with coronary heart disease. Aging Clin Exp Res.2011;23(3):112-117. doi: 10.3275/7041.
An T, Hao J, Li R, Yang M, Cheng G, Zou M. Efficacy of statins for osteoporosis: a systematic review and met-analysis. Osteoporos Int. 2017;28(1):47-57. doi: 10.1007/s00198-016-3844-8.
Munson JC, Bynum JP, Bell J, et al. Patterns of prescription drug use before and after fragility fracture. JAMA Intern Med. 2016;176(10):1531-1538. doi: 10.1001/jamainternmed.2016.4814.
Saag KG, Agnesdei D, Hans D, et al. Trabecular bone score in patients with chronic glucocorticoid therapy-induced osteoporosis treated with alendronate or teriparatide. Arthritis Rheumatol. 2016;68(9):2122-2128. doi: 10.1002/art.39726.
Chuang MH, Chuang TL, Koo M, Wang YF. Trabecular bone score reflects trabecular microarchitecture deterioration and fragility fracture in female adult patients receiving glucocorticoid therapy: A pre-post controlled study. BioMed Res Int. 2017. doi: 10.1155/2017/4210217.
Andersen BN, Johansen PB, Abrahamsen B. Proton pump inhibitors and osteoporosis. Curr Opin Rheumatol. 2016;28(4):420-425. doi: 10.1097/BOR.0000000000000291.
Jacob L, Hadji P, Kostev K. The use of proton pump inhibitors is positively associated with osteoporosis in postmenopausal women in Germany. Climacteric. 2016; 19(5):478-481. doi: 10.1080/13697137.2016.1200549.
Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fracture. Can Med Assoc J. 2008;179:319-326. doi: 10.1503/cmaj.071330.
Lee RH, Lyles KH, Colon-Emeric C. A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. Am J Geriatr Pharmacother. 2010;8(1):34-46. doi: 10.1016/j.amjopharm.2010.02.003.
Arora E, Singh H, Gupta YK. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention. J Family Med Prim Care. 2016;5(2):248-253. doi: 10.4103/2249-4863.192338.
Maghraoui AE, Roux C. DXA scanning in clinical practice. Q J Med. 2008;101(8):605-617. doi: 10.1093/qjmed/hcn022.
Watts NB, Lewiecki EM, Miller PD, Baim S. National osteoporosis foundation 2008 clinician’s guide to prevention and treatment of osteoporosis and the world health organization fracture risk assessment tool (FRAX): What they mean to the bone densiometrist and bone technologist. J Clin Densitom. 2008;11(4):473-477. doi: 10.1016/j.jocd.2008.04.003.
MacLean C, Newberry S, Maglione M, et al. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2007;148(3):197-213. doi: 10.7326/0003-4819-148-3-200802050-00198.
Beaton DE, Vidmar M, Pitzul KB, et al. Addition of a fracture risk assessment to a coordinator’s role improved treatment rates within 6 months of screening in a fragility fracture screening program. J Am Geriatr Soc. 2017; 28(3):863-869. doi: 10.1007/s00198-016-3794-1.
U.S. Preventative Services Task Force. Screening for osteoporosis. Ann Intern Med. 2011;154(5):356-364. doi: 10.7326/0003-4819-154-5-201103010-00307.
Sunyecz JA. The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag. 2008;4(4):827-836.
Eastell, R. (1998). Treatment of postmenopausal osteoporosis. N Engl J Med. 1998;338:736-746. doi: 10.1056/NEJM199803123381107.
Cosman F, de Beur SJ, LeBoff MS, et al, National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2381. doi: 10.1007/s00198-014-2794-2.
Black DM, Schartz AV, Ensrud KE, et al, doi:10.1001/jama.296.24.2927.
Schmidt GA, Horner KE, McDanel DL, Ross MB, Moores KG. Risks and benefits of long-term bisphosphonate therapy. Am J Health Syst Pharm. 2010;67(12):994-1001. doi: 10.2146/ajhp090506.
Kraenzlin, ME, Meier C. Parathyroid hormone analogues in the treatment of osteoporosis. Nat Rev Endocrinol. 2011;7(11):647-656. doi: 10.1038/nrendo.2011.108.
Miller P, Hattersley G, Riis B, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis. JAMA. 2016;316(7):722-733. doi: 10.1001/jama.2016.11136.
TYMLOS^TM[prescribing information]. Waltham, MA: Radius Health, Inc; 2017.
Tetsunaga T, Tetsunaga T, Nishida K, et al. Denosumab and alendronate treatment in patients with back pain due to fresh osteoporotic vertebral fractures. J Orthop Sci. 2017;22(2):230-236. doi: 10.1016/j.jos.2016.11.017.
Recker, RR, Mitlak BH, Ni X, Krege JH. Long-term raloxifene for postmenopausal osteoporosis. Curr Med Res Opin. 2011;27(9):1755-1761. doi: 10.1185/03007995.2011.606312.
Yildirim K, Gureser G, Karatay S, et al. Comparison of the effects of alendronate, risedronate and calcitonin treatment in postmenopausal osteoporosis. J Back Musculoskelet Rehabil.2005;18(3/4):85-89. doi: 10.3233/BMR-2005-183-405.
Christensen L, Iqbal S, Macarios D, Badamgarav E, Harley C. Cost of fractures commonly associated with osteoporosis in a managed-care population. J Med Econ. 2010;13(2):302-313. doi: 10.3111/13696998.2010.488969.

Patellofemoral Instability in the Skeletally Immature Patient: A Review and Technical Description of Medial Patellofemoral Ligament Reconstruction in Patients with Open Physes

Fragility Fractures: Diagnosis and Treatment

References

TREATMENT

NONPHARMACOLOGIC

PHARMACOLOGIC

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