After adjusting for age, sex, and race/ethnicity, the prevalence of osteoporosis at either the femoral neck or lumbar spine is estimated to be 10.3% among adults age 50 years and older, representing more than 10 million people in the United States.1 (Reference Table 5.1 PDF [2] CSV [3])

Women have higher rates of osteoporosis at either of these two skeletal sites than men in the same age group across all ages: the prevalence of osteoporosis in adults age 50 years and older was 4.3% in men and 15.4% in women. Age is an even greater factor than sex in prevalence rates, particularly among women. Women ages 50 years to 59 years have a prevalence of 6.8%, while the prevalence increases to 34.9% for women age 80 years and older. Men show a similar, but less dramatic increase, with prevalence increasing from 3.4% among those ages 50 years to 59 years to 10.9% among men age 80 years and older. (Reference Table 5.1 PDF [2] CSV [3])

The prevalence of osteoporosis by race and ethnicity differs somewhat by BMD measurement site. Non-Hispanic Blacks have the lowest prevalence when based on BMD at either the hip or the spine, while Mexican Americans have the highest prevalence. However, when looking at the two skeletal sites separately, the group with the highest prevalence differs. Mexican Americans have the highest prevalence of osteoporosis if based on the lumbar spine BMD alone, but Non-Hispanic Whites have the highest prevalence if based on the femoral neck BMD alone.1 (Reference Table 5.1 PDF [2] CSV [3])

• 1. a. b. Wright NC, Looker AC, Saag KG, et al.: The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. JBMR 2014;29(11):2520-2526. DOI: 10.1002/jbmr.2269.

Using the current prevalence estimates of osteoporosis based on the NHANES BMD measurements at either the femoral neck or lumbar spine and future US Census projections, the number of people with osteoporosis will increase from an estimated 10.2 million in 2010 to 13.6 million people in 2030, with low bone mass, which may be a precursor to osteoporosis, increasing from 43.4 million people to 57.8 million over the same time frame.1

Although the prevalence of clinically diagnosed osteoporosis is projected to increase further, it is not clear whether the increase reflects an increase in diagnosis or an increase in the actual prevalence of the condition. Specifically, a comparison of femoral neck data from NHANES between 1988 and 1994 and 2005 and 2008 showed an increase in femoral neck BMD and a decline in prevalence of osteoporosis during this time. The observed differences in participant demographics and DXA methods between these NHANES surveys did not completely explain the observed increase in femoral neck BMD. Furthermore, data from NHANES 2005–2010 indicate that both mean femoral neck BMD and total lumbar spine BMD have remained stable during this five-year period among those age 50 years and older.  

However, as noted in the introduction to osteoporosis, the diagnosis can also be made based on fragility fracture, which could also play a role in the discrepancy observed between secular trends in the prevalence of clinically diagnosed osteoporosis versus BMD-defined osteoporosis based on femoral neck data from NHANES.2

• 1. Wright NC, Looker AC, Saag KG, et al.: The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. JBMR 2014;29(11):2520- 2526. Doi: 10.1002/jbmr.2269.
• 2. Looker AC,  Melton LJ, Borrud LG, Shepherd JA: Changes in femoral neck bone density in US adults between 1988-1994 and 2005-2008: Demographic patterns and possible determinants. Osteoporosis International 2012;23:771-780.

International Classification of Diseases (ICD) codes are often used in studies to define conditions in records of national health databases. However, health care providers may include codes that are not primary to the condition being treated, or may make errors in the coding process. Nevertheless, analysis of medical conditions based on ICD diagnosis or treatment codes is the most frequently used basis for health conditions research. Osteoporosis is identified with the ICD code of 733.

Data from the Agency for Healthcare Research and Quality Medical Expenditures Panel Survey [4] (MEPS) is used to estimate the economic burden [5] (cost) of musculoskeletal diseases throughout this site. The MEPS is the only US database to include actual cost paid by insurance companies and patients for the health care they receive.

Using the MEPS data, the prevalence of people with diagnosed osteoporosis has risen as the population ages. The number of persons in the population with an osteoporosis condition rose from 3.2 million to 6.5 million between 1996 and 1998 and 2009 and 2011, nearly doubling the number of people with osteoporosis. This number is lower than the 10 million estimated prevalence for people age 50 years and older reported based on BMD [6].

People between the ages of 45 years and 64 years experienced the steepest rise in osteoporosis diagnosis, increasing from 32% to 35% of all people with osteoporosis in the late 1990s to more than 40% in recent years. (Reference Table 10.1 PDF [7] CSV [8])

A recent report using Medicare data showed an overall increase of 18 percentage points in the number of Medicare beneficiaries with diagnosed osteoporosis, based on ICD-9-CM codes, between 2008 and 2010.1

• 1. Erdem E: Prevalence of chronic conditions among Medicare Part A beneficiaries in 2008 and 2010: Are Medicare beneficiaries getting sicker? Prev Chronic Dis 2014;11:130118. DOI: http://dx.doi.org/10.5888/pcd11.130118 [9].

There is no one national database that captures the number of all hip and spinal fractures and estimates how many additional people have fractures without BMD-defined osteoporosis. The Centers for Disease Control and Prevention have estimated at least 250,000 people age 65 years and older are hospitalized for hip fractures each year, using the National Hospital Discharge Survey (NHDS). Nearly all (95%) hip fractures are caused by falling, usually falling sideways.1

Another comprehensive database for evaluation of the total number of hospitalized fractures is the Agency for Healthcare Research and Quality’s (AHRQ) Nationwide Inpatient Sample [10] (NIS), and is used throughout this site to estimate burden. The NIS includes more than 8 million inpatient hospitalizations each year from all payers in the United States, and is representative of 95% of all hospitalizations in the US. Among women 55 years and older, there were almost 1.7 million hospitalizations for fragility fractures in 2011. Hip fractures were the most common (23%) fractures requiring hospitalization, representing 325,200 hip fractures. Hospitalizations for clinically evident spine fractures (8.4%), representing 245,800 patients, was the second most common type of fragility fracture. For 92% of hospitalizations for hip fracture, this was the primary, or first, diagnosis; for spine fractures, 46% were the primary diagnosis. (Reference Table 5.2.1 PDF [11] CSV [12])

Relying on hospitalized fractures may underestimate the true prevalence of fragility fractures in the United States, since many fractures do not require hospital treatment and approximately two-thirds of all vertebral fractures are not clinically diagnosed.2 An analysis of the AHRQ NIS and National Emergency Department Sample (NEDS), and the CDC National Center for Health Statistics National Hospital Ambulatory Medical Care Survey (NHAMCS–Outpatient) and National Ambulatory Medical Care Survey (NAMCS–Physician Offices) for the years 2010 and 2011, showed 4.3 million fragility fracture visits, of which only 18% were hospital discharge visits. Wrist and arm fractures are the most likely fragility fractures to be treated outside a hospital. (Reference Table 5.2.1 PDF [11] CSV [12])

• 1. Centers for Disease Control and Prevention: Home and Recreational Safety. Hip Fractures Among Older Adults.Available at: http://www.cdc.gov/homeandrecreationalsafety/falls/adulthipfx.html. [13] Accessed September 29, 2015.
• 2. Singer A, Exuzides A, Spangler L. et al.: Burden of illness for osteoporotic fractures compared with other serious diseases among postmenopausal women in the United States. Mayo Clin Proc 2015 Jan;90(1):53-62. doi: 10.1016/j.mayocp.2014.09.011. Epub 2014 Dec 4.

Women are more likely than men to have an osteoporosis diagnosis and to have a fragility fracture. Hospital discharges in 2011 with a fragility fracture diagnosis for women were more than twice the number of discharges in men with the same diagnosis (404,300 discharges for women; 159,500 discharges for men). This difference is evidenced for fragility fractures at all sites, and is also representative of emergency department (ED) visits with a fragility fracture diagnosis.

Age also is a major factor among people diagnosed with a fragility fracture, with people aged 80 years and older representing twice the rate of those between the ages of 70 and 79 years.

Overall, hospital discharges for fragility fractures accounted for 2.6% of hospital discharges for any diagnosis in 2011, and 2.0% of all ED visits. Among women, fragility fractures accounted for 3.5% of all hospital discharges and 2.6% of all ED visits. Among people aged 80 years and older, fragility fractures accounted for 6.4% of all hospital discharges and 4.9% of all ED visits. (Reference Table 5.2.2 PDF [14] CSV [15])

A more detailed discussion of sex and age differences in osteoporosis and fragility fractures can be found in the Special Populations section of this site in Sex and Gender [16] and Aging [17].

Although the number of hospital discharges for hip fractures has increased in recent years due to an aging population, several studies indicate a decreasing rate of hip fractures among white women and men, both in the United States and worldwide, by as much as an annualized 1.5% per year since the early 1990s.1^,2^,3^,4^,5 One recent study reports a reduction in the 10-year hip fracture probability for the white population, based on an updated study of hospital discharges using the National Inpatient Sample (NIS).6

The most recent national examination of hip fracture trends shown a decline in the age-adjusted incidence rate of fracture of 24.5% in women and 19.2% in men from 1995 to 2005.7 Racial and ethnic differences in the declines in hip fractures incidence have been evaluated. For example, a Medicare population study of hip fractures between 2000 and 2009 reported statistically significant declines in White men and women; however, due to smaller numbers, a decline among Black and Hispanic women is not statistically supported.8 Another study of hip fractures among Hispanics reported an increase in hip fractures in this population.9 Given these declines, the US version of the 10-year fracture probability calculator, FRAX, has been undated.

While declines in hip fracture incidence is being observed, fractures remain a concern because there is some indication the reduction in hip fractures is being offset with fractures in other sites, particularly vertebral fractures, due in large part to extended longevity.4

• 1. Gehlback SH, Avrunn JS, Puleo E: Trends in hospital care for hip fractures. Osteoporosis Int 2007;18(5):585-491. Epub 2006 Dec 5.
• 2. Melton LJ 3rd, Kearns AD, Atkinson EJ, et al.: Secular trends in hip fracture incidence and recurrence. Osteoporosis Int 2009;20(5):687-694. doi: 10.1007/s00198-008-0742-8.
• 3. Kanis JA, Odén A, McCloskey EV, et al.: A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporosis Int 2012. doi: 10.1007/s00198-012-1964-3.
• 4. a. b. Shreyasee A, Achenback SJ, Atkinson EJ, et al.: Trends in fracture incidence: A population-based study over 20 years. JBMR 2014;29(3):581-589. doi: 10.1002/jbmr.2072.
• 5. Stevens JS, Rudd RA: Research letter: Declining hip fracture rates in the United States. Age Ageing. 2010;39(4):500-503. doi: 10.1093/ageaging/afq044.
• 6. Ettinger B, Black DM, Dawson-Hughes B, et al.: Updated fracture incidence rates for the US version of FRAX®. Osteoporos Int 2010;21(1):20-33. doi: 10.1007/s00198-009-1032-9.
• 7. Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB: Incidence and mortality of hip fractures in the United States. JAMA 2009;302:1573-1579. doi: 10.1001/jama.2009.1462.8
• 8. Wright NC, Saag KG, Curtis JR, et al.: Recent trends in hip fracture rates by race/ethnicity among older US adults. JBMR 2012;27(11):2325-2332. doi: 10.1002/jbmr.1684.
• 9. Zingmond DS, Melton LJ 3rd, Silverman SL: Increasing hip fracture incidence in California Hispanics, 1983 to 2000. Osteopoross Int 2004;15(8):603-610. Epub 2004 Mar 4.

While the incidence of hip fracture appears to have declined overall since the mid 1990s, as discussed in a previous section [18], hospital discharges from the MEPS database related to osteoporosis were 44% greater in 2009 to 2011 than they were in the years from 1996 to 1998. Recent years, however, have shown a decline after peaking in 2001 to 2003. (Reference Table 10.2 PDF [19] CSV [20]) This increase in hospitalizations likely reflects the increase in older population cohorts as the Boomer generation enters the prime years for fracture incidence.

In a study among Medicare beneficiaries, the 65 years and older population, experiencing hip fractures in the years 2000 to 2004, 98.2% were hospitalized in the six months following the fracture compared to 27.1% hospitalized at least once in the prior six months for other reasons.1 Thus, hip fractures were associated with a 71% increase in the probability of being hospitalized. The average length of stay for hip and upper leg (femur) fractures was more than 11 days. (Reference Tables 5.3 PDF [21] CSV [22] and 5.4 PDF [23] CSV [24])

Using recent 2011 data from the NIS hospital discharge database, an average hospital stay of 5.5 days was reported for people age 50 years and older with a primary (first) diagnosis of fragility fracture. While it might be assumed the inclusion of younger-age patients could account for this difference from the earlier study, age was not a factor in length of stay. Sex was a more significant factor, with males staying nearly a day longer than females. With the exception of wrist and arm fractures, site of the fracture was also not a factor. (Reference Table 5.5 PDF [25] CSV [26])

• 1. Becker DJ, Yun H, Kilgore ML, et al.: Health services utilization after fractures: Recent evidence from Medicare. J Gerontol A Biol Sci Med Sci 2010 Sep;65(9):1012-1020. PMID: 20530242

Patterns similar to hospitalization for the Medicare population were reported for use of skilled nursing facility and home health services following hospitalization before and after fractures, although the rates for these services were somewhat lower. Hip fractures were associated with an 84% increase in probability of a stay in a skilled nursing facility.1 (Reference Tables 5.3 PDF [21] CSV [22] and 5.4 PDF [23] CSV [24])

• 1. Becker DJ, Yun H, Kilgore ML, et al.: Health services utilization after fractures: Recent evidence from Medicare. J Gerontol A Biol Sci Med Sci 2010 Sep;65(9):1012-1020. PMID: 20530242

In a recent study, the effect of fracture on physician office visits using a baseline of visits six months before fracture and comparing it to six months after fracture, was less than for hospitalization, but still substantial.1 Fractures of the tibia/fibula had the greatest increase in physician office visits (35% increase in probability of a visit), but this could be because of higher rates of transfer to nursing home care for hip, pelvis, and femur fractures shown in studies discussed previously. (Reference Table 5.6 PDF [27] CSV [28])

Following fractures, utilization of physical and occupational therapy services increased by similar proportions.1

Although the mean number of ambulatory physician visits for osteoporosis care from the MEPS study, the data upon which estimated cost burden from osteoporosis [5] is based, declined between 1996 and 1998 and between 2009 and 2011, the total number of visits over this timeframe increased by 67% because of the larger number of people with osteoporosis. Because the MEPS data is based on only an osteoporosis diagnosis rather than a fracture diagnosis, the actual numbers may be larger than reported.

Again, using the MEPS, the mean number of home health visits for osteoporosis between 1996 and 1998 was 7.7; from 2009 to 2011 it was 7.4. However, the total number of visits rose from 24.3 million to 47.5 million due to the rise in reported prevalence of osteoporosis. Ambulatory nonphysician health care visits nearly tripled, increasing from 10.7 million to 28.9 million, due to an increase in both mean number of visits and the share of persons with reported osteoporosis who made at least one such visit. (Reference Table 10.2 PDF [19] CSV [20])

• 1. a. b. Tajeu GS, Delzell E, Smith W, et al.: Death, debility, and destitution following hip fracture. J Gerontol A Biol Sci Med Sci 2014 Mar;69(3):346-353. PMID: 23873945

Serious adverse outcomes following hip fractures include mortality, debility requiring institutional care, and destitution (poverty) sufficient to qualify for Medicaid enrollment. In a recent study of Medicare beneficiaries, the population age 65 years and older, individuals experiencing hip fracture had more than double the risk of death, an almost four-fold increased risk of becoming a nursing home resident, and more than double the risk of enrolling in Medicaid within one year of the fracture.1 (Reference Table 5.7 PDF [29] CSV [30])

Two recent studies of the Medicare population support a significant decline in mortality from hip fractures in recent years, with reported mortality rates of 22%2 and 30%3 in the first year following fracture. However, hip fracture remains a major mortality risk 2- to 8-fold higher than non-hip-fracture matched controls.3

• 1. Tajeu GS, Delzell E, Smith W, et al.: Death, debility, and destitution following hip fracture. J Gerontol A Biol Sci Med Sci 2014 Mar;69(3):346-353. PMID: 23873945
• 2. Lo JC, Srinivasan S, Chandra M: Trends in mortality following  hip fracture in older women. Am J Manag Care 2015;21(3):e206-e214. Published online: April 15, 2015.
• 3. a. b. Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB: Incidence and mortality of hip fractures in the United States. JAMA 2009;302(14):1573-1579. doi: 10.1001/jama.2009.1462.

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. [35] Accessed August 2015.

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.

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 [36]. 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.

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 [37]. 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 [38]. 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.

There are three new drugs being tested as potential osteoporosis treatments.

Abaloparatide

Abaloparatide is an analog of parathyroid hormone-related protein (PTHrP) being developed as a potential anabolic agent for osteoporosis treatment. In a phase 2 study, abaloparatide increased BMD at the lumbar spine, femoral neck, and total hip in a dose-dependent fashion. The abaloparatide-induced BMD increases either trended to or were significantly greater than those seen with teriparatide. Phase 3 studies will evaluate fracture outcome and additional safety with this therapy.

Odanacatib

Odanacatib is a selective inhibitor of cathepsin K, a collagenase produced by osteoclasts and responsible for the degradation of bone mineral and matrix. Women receiving odanacatib for five years gained BMD at the spine and hip, and showed bone biomarker changes somewhat different from those seen with bisphosphonates and typical antiresorptive therapies.1^,2 Also in contrast with bisphosphonates, after odanacatib discontinuation there was rapid reversal of treatment effects. Although the safety profile has been mild, cathepsin inhibitors have been associated with a scleroderma-like skin lesion. Other potential safety signals are being further investigated.

Anti-sclerostin antibodies

Sclerostin is produced by osteocytes and inhibits anabolic signaling pathway important for bone formation. Rare natural deficiencies in sclerostin result in sclerosing bone diseases, sclerosteosis, and van Buchem disease, which are radiographically characterized by thickened bones, including all long bones. Monoclonal antibodies to sclerostin are being investigated for both osteoporosis treatment and for fracture healing. Preliminary studies suggest a significant increase in BMD with the anti-sclerostin romosuzumab.3 Phase 3 clinical trials evaluating fracture risk protection are underway.

• 1. Eisman JA, Bone HG, Hosking DJ, et al.: Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three-year continued therapy and resolution of effect. J Bone Miner Res 2011 Feb;26(2):242-251. doi: 10.1002/jbmr.212.
• 2. Langdahl B, Binkley N, Bone H, et al.: Odanacatib in the treatment of postmenopausal women with low bone mineral density: Five years of continued therapy in a phase 2 study. J Bone Miner Res 2012 Nov;27(11):2251- 2258. doi: 10.1002/jbmr.1695.
• 3. McClung MR, Grauer A, Boonen S, et al.: Romosozumab in postmenopausal women with low bone mineraldensity. N Engl J Med 2014;370:412-420. doi: 10.1056/NEJMoa1305224.

Coordination of acute postfracture care with subsequent secondary osteoporosis prevention and treatment is a tenet of good osteoporosis management. Although most people who experience a fracture receive excellent and appropriate acute care management in a hospital or emergency department, most are not subsequently referred to or do not pursue postfracture osteoporosis care with a bone health specialist.

The fracture liaison service (FLS) is a model of care developed in Europe and successfully implemented in a number of US managed health care systems that seeks to facilitate postfracture care coordination. FLS operates under the supervision of bone health specialists and collaborates with primary care, orthopedic, and emergency department health care providers. Care typically is coordinated postfracture through a nurse or other allied health professional. Patients with recent fractures are tracked via a registry, and timelines are established for postfracture assessments and follow-ups. FLS programs recognize that patients who have fractured are at highest risk of future fractures. FLS programs in certain settings have reduced the number of fractures and have achieved cost savings by identifying and appropriately treating postfracture patients.

The efficiency of the FLS approach varies depending on its intensity and potentially the location of its implementation.1^,2

• 1. Ganda K, Puech M, Chen JS, et al.: Models of care for the secondary prevention of osteoporotic fractures: A systematic review and meta-analysis. Osteoporos Int 2013 Feb;24(2):393-406. doi: 10.1007/s00198-012-2090-y. Epub 2012 Jul 25.
• 2. Solomon DH, Patrick AR, Schousboe J, Losina E: The potential economic benefits of improved post-fracture care: A cost-effectiveness analysis of a fracture liaison service in the US healthcare system. J Bone Miner Res 2014 Jul;29(7):1667-1674. doi: 10.1002/jbmr.2180.

The National Institutes of Health (NIH) supports both basic and clinical investigation in osteoporosis. Within the NIH, the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS); the National Institute on Aging (NIA); the National Institute of Dental and Craniofacial Research (NIDCR); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); and The National Institute of Child Health and Human Development (NICHD) all support osteoporosis-related research. NIAMS [39], the top institute for osteoporosis research, reported $72 million in osteoporosis research funding in fiscal year 2014, with an NIH-wide total of $141 million for osteoporosis-related projects.1 Additional research support is provided by other federal agencies including the Agency for Health Care Research and Quality [40] (AHRQ), the Centers for Disease Control and Prevention [41] (CDC), and the Veterans Administration Research [42] program. The new Patient-Centered Outcomes Research Institute [43] (PCORI) has also supported osteoporosis research. The top private and agency funds for osteoporosis include the American Society of Bone and Mineral Research [44]and the American College of Rheumatology [45]. Although numerous agencies fund osteoporosis research, the dollars available are limited in comparison to other conditions prevalent in older Americans. Additional research funding would assist in identifying treatments, management strategies, and factors that can minimize the burden associated with osteoporosis.

• 1. National Institutes of Health, NIH Categorical Spending: Estimates of funding for various research, condition, and disease categories (RCDC). Available at: http://report.nih.gov/categorical_spending.aspx [46]. Accessed August 8, 2015.