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Key Challenges to Future

V.E.0

Lead Author(s): 

Nicole C. Wright, PhD, MPH

There are many challenges in osteoporosis healthcare and delivery that need to be addressed in the future, including but not limited to screening, pharmacotherapy use, pharmacotherapy adherence, and addressing osteoporosis care in patients with multiple comorbidities.

Edition: 

  • 2014

Osteoporosis Screening

V.E.1

Lead Author(s): 

Nicole C. Wright, PhD, MPH

Screening and treating at-risk patients can prevent fractures and reduce the morbidity associated with osteoporosis. Over the last few years, rates of osteoporosis screening via DXA testing have steadily declined in the US. The initial decline in 2006 was associated with reductions in the DXA reimbursement rates by Medicare. Fewer DXA scans were performed in 2007 and 2008 than the number projected using Commercial and Medicare Supplemental Insurance data from 2000 to 2006,1 and similar declines were observed in Medicare Fee-for-Service population.2 More recently, DXA examination rates were studied in women aged 50 years to 64 years, and the authors found reductions in the number of DXA scans performed between 2006 and 2012 (-35 DXAs per 1,000 patient years) in this younger population, with the most significant reduction (-33%) in the 50- to 54-year age group.3

The reduction in overall DXA screening is also affecting the high-risk fracture patient population. The use of DXA postfracture is low. In one Midwestern county hospital, only 10% of hip fracture patients had a DXA ordered upon hospital discharge.4 Only 10% of Medicare beneficiaries who sustained a major osteoporotic fracture received postfracture DXA testing,5. Four well-established Midwestern health care systems reported less than one-quarter of patients who had a hip fracture had bone density testing before or after their fracture.6 This data was corroborated by national Healthcare Effectiveness Data and Information Set (HEDIS) measures, demonstrating that less than one-third of people postfracture have received testing or treatment.7

  • 1. O'Malley CD, Johnston SS, Lenhart G, et al.: Trends in dual-energy X-ray absorptiometry in the United States, 2000–2009. J Clin Densitom 2011 Apr-Jun;14(2):100-107. doi: 10.1016/j.jocd.2011.03.003.
  • 2. Zhang J, Delzell E, Zhao H, et al.: Central DXA utilization shifts from office-based to hospital-based settings among medicare beneficiaries in the wake of reimbursement changes. J Bone Miner Res 2012 Apr;27(4):858-864. doi: 10.1002/jbmr.1534.
  • 3. Overman RA, Farley JF, Curtis JR, et al.: DXA utilization between 2006 and 2012 in commercially insured younger postmenopausal women. J Clin Densitom 2015 Apr-Jun;18(2):145-149. doi: 10.1016/j.jocd.2015.01.005. Epub 2015 Feb 18.
  • 4. Antonelli M, Einstadter D, Magrey M.: Screening and treatment of osteoporosis after hip fracture: Comparison of sex and race. J Clinic Densitometry 2014;17(4):479-483. doi: 10.1016/j.jocd.2014.01.009. PMID: 24657109.
  • 5. Liu SK, Munson JC, Bell JE, et al.: Quality of osteoporosis care among older medicare fragility fracture patients 2006–2010. J Am Geriatr Soc 2013 Nov;61(11):1855-1862. Published online 2013 Oct 28. doi: 10.1111/jgs.12507.
  • 6. Harrington JT, Broy SB, Derosa AM, et al.: Hip fracture patients are not treated for osteoporosis: A call to action. Arthritis Rheum 2002 Dec 15;47(6):651-654.
  • 7. National Committee on Quality Assurance: The state of health care quality 2014. 2014:90-91. Available at: http://www.ncqa.org/ReportCards/HealthPlans/StateofHealthCareQuality.aspx. [1] Accessed August 2015.

Edition: 

  • 2014

Osteoporosis Pharmacotherapy

V.E.2

Lead Author(s): 

Nicole C. Wright, PhD, MPH
Kenneth S. Saag, MD, MSc

Currently, the pharmacotherapies approved for the treatment and prevention of osteoporosis fall under two categories: antiresorptive and anabolic agents. The antiresorptive agents inhibit the action of bone cells that degrade bone, whereas the anabolic agents promote bone formation. Teriparitide is the only approved anabolic agent. There are a number of FDA- approved classes of antiresporptive agents including bisphosphonates, selective-estrogen receptor modulators (SERMS), receptor activator of nuclear factor kappa beta (RANK) ligand inhibitors, and estrogen. The bisphosphonates are the most commonly used agents, which include oral (alendronate, ibandronate, and risedronate) and parenteral (ibandronate and zoledronic acid) preparations.  

All of these agents have been shown to reduce the risk of vertebral fracture. Some of these have been shown also to reduce the risk of nonvertebral fractures, in some cases including hip fracture. Large randomized, placebo-controlled studies suggest that there is a 30% to 70% reduction in the risk of vertebral fractures and a 16% to 25% reduction in the risk of nonvertebral fractures with pharmacologic treatment.1,2 A number of general recommendations can be made regarding pharmacologic therapy for osteoporosis:

  • Bisphosphonates are usually considered first-line treatment for osteoporosis, particularly because of their positive effects on vertebral, nonvertebral, and hip fractures.

  • Second-line options include denosumab, raloxifene, strontium ranelate (in countries where available), and teriparatide.

  • Teriparatide use is often confined to high-risk patients, those with fractures, and in those with glucocorticoid- induced osteoporosis. Risk of osteosarcoma limits administration to two years.

  • Largely in light of the Women’s Health Initiative (WHI) study results and the availability of many other efficacious compounds, estrogen is no longer considered first-line therapy.

  • Combination use of antiresorptive drugs is generally not recommended because there is no current evidence of additional antifracture benefits, and there may be an increased risk of side effects and the over-suppression of bone turnover.

Patients deemed appropriate candidates for a pharmacologic therapy include:

  • Men and women who have experienced a hip or spine fracture

  • Those with osteoporotic range BMD determined by DXA

  • Persons with low bone mass (osteopenia) meeting a fracture risk (FRAX) threshold  of more than 3%  for hip and more than 20% for major osteoporotic fracture, based on the National Osteoporosis Foundation (NOF) recommendations3

  • Selected individuals without low bone mass but high fracture risk due to risk states such as use of glucocorticoids

Fracture risk thresholds may be different outside the United States.

Although a number of agents are available, the use of osteoporosis pharmacotherapy is also declining. Using commercial dispensing data, the use of oral bisphosphonates, the most commonly prescribed anti-osteoporosis pharmacotherapy, decreased by more than 50% from a peak of 31 million prescriptions dispensed in 2007 to only 14.7 million in 2012.4 Although less drastic, the sales of parenteral bisphosphonates for osteoporosis have also declined by 22% since its peak of 561,600 units in 2010 to 436,900 in 2012.4 It is speculated that declining treatment rates may be associated with a decrease in osteoporosis screening, lower physician initiation of therapy, and/or patient- or provider-initiated “drug holidays,” which are becoming more common because of perceived safety concerns of long-term bisphosphonate use.

The declining use of pharmacotherapy is also prevalent among those newly diagnosed with osteoporosis. In a recent study among women with incident osteoporosis, more than 64% of women had no indications of osteoporosis pharmacotherapy use one year after diagnosis.5 Pharmacotherapy use in those who have sustained a fracture is low. Recent evaluations have found that only 12% of Medicare beneficiaries had evidence of osteoporosis pharmacotherapy use six months after sustaining a fracture.6 In a managed care population, only 18% of fracture patients had indications for osteoporosis pharmacotherapy within 90 days of their fracture, and only 23% appeared to use osteoporosis pharmacotherapy within a year postfracture.7 Studies in hip fracture patients found that 19% to 24% received therapy within one year postfracture,8,9 and that pharmacotherapy use posthip fracture has declined from 40% in 2002 to 21% in 2011.9

  • 1. Kanis JA1, Burlet N, Cooper C, et al.: European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008 Apr;19(4):399-428. doi: 10.1007/s00198-008-0560-z. Epub 2008 Feb 12.
  • 2. Sambrook P1, Cooper C: Osteoporosis. Lancet 2006 Jun 17;367(9527):2010-2018.
  • 3. Cosman F, deBeur SJ, LeBoff MS, et al.: Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 2014;25(10):2359–2381. doi: 10.1007/s00198-014-2794-2.
  • 4. a. b. Wysowski DK, Greene P.: Trends in osteoporosis treatment with oral and intravenous bisphosphonates in the United States, 2002–2012. Bone 2013;57(2):423-428.
  • 5. Siris ES, Modi A, Tang J, et al.: Substantial under-treatment among women diagnosed with osteoporosis in a US managed-care population: A retrospective analysis. Curr Med Res Opin 2014 Jan;30(1):123-130. doi: 10.1185/03007995.2013.851074. Epub 2013 Oct 25.
  • 6. Liu SK, Munson JC, Bell JE, et al.: Quality of osteoporosis care of older Medicare recipients with fragility fractures: 2006 to 2010. J Am Geriatr Soc 2013 Nov;61(11):1855-1862. doi: 10.1111/jgs.12507. Epub 2013 Oct 28.
  • 7. Wilk A, Sajjan S, Modi A, et al.: Post-fracture pharmacotherapy for women with osteoporotic fracture: Analysis of a managed care population in the USA. Osteoporos Int 2014 Dec;25(12):2777-2786. doi: 10.1007/s00198-014-2827-x. Epub 2014 Aug 12.
  • 8. Antonelli M, Einstadter D, Magrey M.: Screening and treatment of osteoporosis after hip fracture: Comparison of sex and race. J Clinic Densitometry 2014;17(4):479-483. doi: 10.1016/j.jocd.2014.01.009. PMID: 24657109.
  • 9. a. b. Solomon DH, Johnston SS, Boytsov NN, et al.: Osteoporosis medication use after hip fracture in US patients between 2002 and 2011. J Bone Miner Res 2014 Sep; 29(9):1929-1937. Published online 2014 Aug 20. doi:  10.1002/jbmr.2202 PMCID: PMC4258070.

Edition: 

  • 2014

Adherence to Osteoporosis Pharmacotherapies

V.E.3

Lead Author(s): 

Nicole C. Wright, PhD, MPH

Low adherence to osteoporosis pharmacotherapies has been documented since bisphosphonates first became available in 1995. Less than 50% of patients starting an oral bisphosphonate are still receiving this drug one year later.1 The early formulations had strict dosing instructions and significant gastrointestinal side effects. The availability of parenteral preparations (intravenous [IV] zoledronic acid and ibandronate) and later formulations improved adherence rates, but even with these agents, adherence rates are not at 100%. Only 32% of IV zoledronic acid users received their second annual dose, and nearly 20% of IV ibandronate users received only one of the four annual doses.2  Mechanisms to improve adherence to medications include engaging pharmacists in patient education activities to encourage adherence.3,4 In Kaiser Permanente Colorado, an interactive voice response (IVR) reminder system followed by a personalized letter for patients prescribed osteoporosis medications led to increased medication purchase in the short term but did not change the medication adherence in the long term.5 Additional efforts targeting patients, providers, and the health system are needed to improve adherence to osteoporosis medications.

  • 1. Curtis JR, Westfall AO, Allison JJ, et al.: Channeling and adherence with alendronate and risedronate among chronic glucocorticoid users. Osteoporos Int 2006;17(8):1268-1274. Epub 2006 May 19.
  • 2. Curtis JR, Yun H, Matthews R, et al.: Adherence with intravenous zoledronate and intravenous ibandronate in the United States Medicare population. Arthritis Care Res (Hoboken) 2012 Jul;64(7):1054-1060. doi: 10.1002/acr.21638.
  • 3. Murphy-Menezes M: Role of the pharmacist in medication therapy management services in patients with osteoporosis. Clinical Therapeutics Jul 2015;37(7);1573-1586. Published Online: April 23, 2015. DOI: Available at: http://dx.doi.org/10.1016/j.clinthera.2015.03.023 [2]. Accessed August 23, 2015.
  • 4. Stuurman-Bieze AG, Hiddink EG, van Boven JF, Vegter S.: Proactive pharmaceutical care interventions decrease patients' nonadherence to osteoporosis medication. Osteoporos Int 2014 Jun;25(6):1807-1812. doi: 10.1007/s00198-014-2659-8. Epub 2014 Feb 26.
  • 5. Cizmic AD, Heilmann RM, Milchak JL, et al.: Impact of interactive voice response technology on primary adherence to bisphosphonate therapy: A randomized controlled trial. Osteoporos Int 2015 Aug;26(8):2131-2136. doi: 10.1007/s00198-015-3116-z. Epub 2015 May 9.

Edition: 

  • 2014

Multimorbidity

V.E.4

Lead Author(s): 

Nicole C. Wright, PhD, MPH

Multiple comorbidities create further challenges in the care of osteoporosis patients. Certain comorbidities and the medications used to treat them could also negatively impact bone health, for example, rheumatoid arthritis and the corticosteroids used in symptom relief. A recent study evaluated the comorbidities of women with and without osteoporosis in the Geisinger Health System.1 Of the comorbidities commonly found among women with osteoporosis compared to women without osteoporosis, two have known independent and/or drug-related adverse effects on bone. Gastroesophageal reflux disease (GERD) was found in 55.6 per 1,000 person-years in women with osteoporosis versus 40.3 per 1,000 person-years in those without, while depression was found in 46.8 versus 36.9 per 1,000 person-years in the respective groups.1 Diagnosed depression,2,3 depressive symptoms,4,5,6,7,8 and medications used to treat depression9,10,11,12,13 have been associated with osteoporosis and fractures. Proton Pump Inhibitors (PPIs) are a common GERD treatment. The use of PPIs, particularly at high doses, has been associated with higher overall fracture risk14,15,16,17,18 and hip fracture risk.19,20,21 Like the prevalence of osteoporosis, the number of comorbidities increases with aging. Comorbidities compete with health care and medication priorities and may contribute to the low adherence levels to osteoporosis drugs.

  • 1. a. b. O'Malley CD, Tran N, Zapalowski C, et al.: Multimorbidity in women with and without osteoporosis: Results from a large US retrospective cohort study 2004–2009. Osteoporos Int 2014 Aug;25(8):2117-2130. doi: 10.1007/s00198-014-2740-3. Epub 2014 May 24.
  • 2. Schweiger U, Deuschle M, Körner A, et al.: Low lumbar bone mineral density in patients with major depression. Am J Psychiatry 1994 Nov;151(11):1691-1693.
  • 3. Lee CW, Liao CH, Lin CL, et al.: Increased risk of osteoporosis in patients with depression: A population-based retrospective cohort study. Mayo Clin Proc 2015 Jan;90(1):63-70. doi: 10.1016/j.mayocp.2014.11.009.
  • 4. Robbins J, Hirsch C, Whitmer R, et al.: The association of bone mineral density and depression in an older population. J Am Geriatr Soc 2001 Jun;49(6):732-736.
  • 5. Wong SY, Lau EM, Lynn H, et al.: Depression and bone mineral density: Is there a relationship in elderly Asian men? Results from Mr. Os (Hong Kong). Osteoporos Int 2005 Jun;16(6):610-615. Epub 2004 Sep 23. PMID: 15448988.
  • 6. Silverman SL, Shen W, Minshall ME, et al.: Prevalence of depressive symptoms in postmenopausal women with low bone mineral density and/or prevalent vertebral fracture: Results from the multiple outcomes of raloxifene evaluation (MORE) study. J Rheumatol 2007;34:140-144.
  • 7. Erez HB, Weller A, Vaisman N, et al.: The relationship of depression, anxiety and stress with low bone mineral density in post-menopausal women. Arch Osteoporos 2012 Dec; 7(1-2):247-255.
  • 8. Diem SJ, Ruppert K, Cauley JA, et al.: Rates of bone loss among women initiating antidepressant medication use in midlife. J Clin Endocrinol Metab 2013 Nov;98(11):4355-4363. doi: 10.1210/jc.2013-1971. Epub 2013 Sep 3.
  • 9. Ensrud KE, Blackwell T, Mangione CM, et al.: Central nervous system active medications and risk for fractures in older women. Arch Intern Med 2003;163(8):949-957. doi:10.1001/archinte.163.8.949.
  • 10. Cauley JA, Fullman RL, Stone KL, et al.: Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int 2005 Dec;16(12):1525-1537. Epub 2005 May 11.
  • 11. Haney EM, Chan BKS, Diem SJ, et al.: Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med 2007;167(12):1246-1251. doi:10.1001/archinte.167.12.1246.
  • 12. Richards JB, Papaioannou A, Adachi JD, et al.: Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 2007;167(2):188-194. doi:10.1001/archinte.167.2.188.
  • 13. Ak E, Bulut SD, Bulut S, et al.: Evaluation of the effect of selective serotonin reuptake inhibitors on bone mineral density: An observational cross-sectional study. Osteoporos Int 2015;26:273–279. doi: 10.1007/s00198-014-2859-2. PMCID: PMC4286623.
  • 14. Vestergaard P, Rejnmark L, Mosekilde L: Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int 2006 Aug;79(2):76-83. Epub 2006 Aug 15.
  • 15. Targownik LE, Lix LM, Metge CJ, et al.: Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ 2008 Aug 12;179(4):319-326. doi: 10.1503/cmaj.071330.
  • 16. Gray SL, LaCroix AZ, Larson J, et al.: Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: Results from the Women's Health Initiative. Arch Intern Med 2010 May 10;170(9):765-771. doi: 10.1001/archinternmed.2010.94.
  • 17. Khalili H, Huang ES, Jacobson BC, et al.: Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: A prospective cohort study. BMJ 2012;344:e372. Available at doi: http://dx.doi.org/10.1136/bmj.e372 [3]. Accessed August 2014.
  • 18. Moberg LME, Nilsson PM, Samsioe G, Borgfeldt C.: Use of proton pump inhibitors (PPI) and history of earlier fracture are independent risk factors for fracture in postmenopausal women. The WHILA study. Maturitas Aug;78(4):310-315. Available at doi: http://dx.doi.org/10.1016/j.maturitas.2014.05.019 [4]. Accessed August 2015.
  • 19. Yang YX, Lewis JD, Epstein S, Metz DC: Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006 Dec 27;296(24):2947-2953.
  • 20. Corley DA, Kubo A, Zhao W, Quesenberry C: Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology 2010 Jul;139(1):93-101. doi: 10.1053/j.gastro.2010.03.055. Epub 2010 Mar 27.
  • 21. Adams AL, Black MH, Zhang JL, et al.: Proton-pump inhibitor use and hip fractures in men: A population-based case-control study. Ann Epidemiol. 2014 Apr;24(4):286-290. doi: 10.1016/j.annepidem.2014.01.004. Epub 2014 Jan 16.

Edition: 

  • 2014
The Burden of Musculoskeletal Diseases in the United States - Copyright © 2014.

Source URL: https://bmus.latticegroup.com/2014-report/ve0/key-challenges-future

Links:
[1] http://www.ncqa.org/ReportCards/HealthPlans/StateofHealthCareQuality.aspx
[2] http://dx.doi.org/10.1016/j.clinthera.2015.03.023
[3] http://dx.doi.org/10.1136/bmj.e372
[4] http://dx.doi.org/10.1016/j.maturitas.2014.05.019