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.
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
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
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.
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.
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