Improving Patients' Outcomes After Osteoporotic Fractures

Rozalia Dimitriou; Giorgio Maria Calori; Peter V Giannoudis

Disclosures

Int J Clin Rheumatol. 2012;7(1):109-124. 

In This Article

Secondary Prevention of Osteoporotic Fractures

As an osteoporotic fracture is the strongest indicator of risk for future fracture and an episode of osteoporotic fracture at least doubles the likelihood of further fractures, the implementation of strategies regarding the assessment and treatment of osteoporosis and the secondary prevention with a falls risk assessment is of great importance in an effort to reduce the risk of further fractures.[1,8] Since orthopedic surgeons are usually the first physicians to assess and treat the patient after a fragility fracture, their role therefore does not end in the treatment of the fracture; but they should also ensure that preventive measures are implemented using a multidisciplinary approach among clinicians, allied healthcare professionals (nurses, physical and occupational therapists and social workers) and administrative staff.[26]

The need for a multidisciplinary approach for postfracture osteoporosis care to ensure treatment is provided routinely with continuity of care is well recognized. It has been shown that implementation of a coordinator-based program can improve postfracture osteoporosis care starting by early identification of these patients and documentation of osteoporosis to allow assessment, referral and appropriate treatment of underlying osteoporosis.[26,27] Such an approach can also be cost effective in avoiding future costs of subsequent fragility fractures.[28] Referrals for rheumatology or endocrinology consultation of postfracture patients can increase the percentage of patients receiving therapy for osteoporosis, and dedicated nurses, geriatricians or family physicians can improve outcomes by increasing, not only initiation, but also adherence to treatment.[29] However, despite the effectiveness of preventive measures, few patients currently receive such services.[8]

Assessment & Treatment of Osteoporosis

Although fracture care is often the first opportunity for clinical management of osteoporosis, many patients do not receive any evaluation after a fracture. Several studies have indicated that investigation for osteoporosis after fracture is less than optimal and patients with low-energy fractures may not even be evaluated or receive any treatment for underlying osteoporosis.[30] Ideally, assessment for osteoporosis should be offered in all these patients as it has been shown that the risk of further fractures in those found to be in the 'osteoporotic range' can be reduced by half by antiresorptive therapy.[1] McLellan et al. demonstrated that by providing routine assessment and, where necessary, treatment for osteoporosis after a fracture as well as specific recommendations for secondary prevention, osteopenic or osteoporotic patients can be successfully identified and treated.[31] Routine diagnostic procedures in osteoporosis evaluation should include history and physical examination, bone density measurement with dual-energy x-ray absorptiometry scan and laboratory tests.[32] However, in older women and men with a fragility fracture over the age of 75 years, bone density measurement is not needed and treatment with bisphosphonates is recommended regardless of bone mineral density (BMD).[33]

Medical Treatment

In general, after diagnosis of osteoporosis, a coordinated postfracture osteoporosis treatment program should be provided for patients with a fragility fracture[26] involving the orthopedic surgeon, rheumatologist or endocrinologist and the family physician. In summary, therapeutic options to reduce hip fracture risk include calcium and vitamin D repletion and osteoporotic medical treatment.[34] The primary goal of pharmacologic treatment of osteoporosis is to reduce the risk of subsequent fractures. Several classes of drugs are currently being used for the prevention and management of postmenopausal osteoporosis, including bisphosphonates, calcitonin, estrogens and/or hormone therapy, raloxifene, strontium ranelate and parathyroid hormone (PTH).[12]

Bisphosphonates are currently used as first-line treatment for osteoporosis, as they increase BMD by reducing the rate of bone resorption and they can be administered either orally or via intravenous infusion, with each mode of administration having associated benefits and costs.[12,35] Bisphosphonates are of proven benefit in the prevention of fragility fractures.[36] In addition to reduced fracture risk, interventions can improve quality of life and reduce mortality in patients with fragility fractures.[37] Recommendations for administration of bisphosphonates include postmenopausal women aged 65–75 years if osteoporosis is confirmed by dual-energy x-ray absorptiometry scan, and older women without the need for a scan. Bisphosphonates are also recommended for postmenopausal women younger than 65 years when they have a very low BMD or extra independent risk factors of further fragility fractures.[36] Regarding hormone replacement therapy, it is not recommended as a first-line therapy for the prevention of osteoporosis.[202]

However, even though bisphosphonates are the most widely used antiresorptive agents for the treatment of osteoporosis, their long-term use has been associated with increased fracture risk for the so-called 'atypical fractures' secondary to suppressed bone turnover, affecting sites such as the subtrochanteric femur that are infrequently affected by osteoporotic fractures.[37,38] It remains unknown whether the pathophysiology of these atypical insufficiency fractures is related to the mode of action of bisphosphonates leading to the accumulation of microfractures and weakening of bone, or whether they represent an unusual osteoporotic fracture manifestation.[38,39] Overall, the optimal duration of bisphosphonate treatment is still unclear and the real risk of associated stress fractures needs to be elucidated. Recently, it has been found that there was no evidence of an increased risk of atypical femur fractures in bisphosphonate users compared with raloxifene/calcitonin users, but the possibility that long-term bisphosphonate use may increase the risk of these fractures cannot be excluded.[40] In the meantime, clinicians should be aware that patients on long-term treatment may develop such fractures and the decision to maintain a patient on therapy beyond 5 years should be taken on a case-by-case approach, guided by assessment of individual overall fracture risk, and the drug's efficacy and safety profile.[39] A 12-month interruption in therapy after 5 years in patients who are clinically stable has been suggested; and in those who sustained an atypical fracture while receiving bisphosphonate therapy, teriparatide treatment is advised.[41]

Another alternative to the antiresorptive drugs that reduce bone turnover is the use of anabolic agents. Currently, teriparatide, a recombinant formulation of PTH, is available as a bone-forming therapy for the treatment of osteoporosis and it has been found to reduce the incidence of vertebral and nonvertebral fractures in osteoporotic patients.[42] Teriparatide is recommended as an alternative treatment option for the secondary prevention of osteoporotic fragility fractures in postmenopausal women who are unable, have a contraindication or are intolerant to bisphosphonates.[36]

Overall, preventive pharmacotherapy reduces the risk of vertebral fracture by 30–70%, depending on the agent and patient's compliance.[43] Furthermore, both calcitonin and teriparatide are also useful in decreasing the pain associated with vertebral fractures.[44,45] However, the effect on nonvertebral fractures is lower and varies by fracture site. For example for hip fractures, the relative reductions in risk in the osteoporosis trials range from 30 to 51%.[46] In a recent meta-analysis assessing the efficacy of different bisphosphonates in the prevention of osteoporotic fractures, it has been found that there is a 47% probability that zoledronic acid shows the greatest risk reduction of hip fractures, followed by alendronate (36%) and risedronate (11%).[47] On the contrary, for wrist fractures, there were no particular antiosteoporotic agents with a significant protective effect versus the other agents or placebo.[42]

Overall, when choosing a particular pharmacological agent it should be kept in mind that agents found to decrease vertebral, nonvertebral and hip fractures should be used preferentially over those that only demonstrate vertebral antifracture efficacy. As a general rule, therapeutic decisions should be based on a balance between benefits and risks of treatment for each particular patient, as no single agent is appropriate for all patients.[46]

Even though it has been shown that treatments can reduce the risk of future fractures,[1] when taken regularly and long term,[48,49] they are usually being used irregularly and suboptimally despite prescription.[50,51] Generally, poor adherence and no persistence in antiresorptive medication regimens are common in patients with osteoporosis, and this can negatively affect patient outcomes and increase the risk of a subsequent fracture. Particularly for oral bisphosphonates, rates of adherence decline dramatically during the first year of treatment and continue to decline thereafter.[52] The alternative use of intravenous administration of zoledronic acid once a year may ensure that patients will have a full treatment effect for at least 12 months.[48] Lack of patients' adherence, including compliance and persistence to the osteoporotic treatment represents an important issue that affects outcome. Even in randomized, controlled clinical trials where patients are carefully monitored and in regular contact with healthcare professionals, the adherence rate varies between 60 and 81%.[53] Furthermore, in the everyday clinical practice, compliance and persistence by patients to treatment of osteoporosis is even lower, and clinicians may have a misconception of how adherent their patients are.[53] There are numerous reasons for lack of patients' adherence including complicated dosing regimens or dosing intervals and lack of knowledge about osteoporosis and the importance of the treatment for fracture prevention. For example, patients are more adherent to monthly versus weekly, and weekly versus daily bisphosphonates. Nevertheless, even with weekly or monthly treatment, patients still had suboptimal adherence.[53] The use of intravenous bisphosphonates such as ibandronate (quarterly dosing) and zoledronic acid (annual dosing) may lead to improved adherence by patients. Furthermore, adverse effects, such as osteonecrosis of the jaw or gastrointestinal irritation, which can be either real or perceived, represent important reasons why patients may not adhere to treatment.[53,54] To maximize adherence, it is important for patients to understand the nature and progression of osteoporosis, even though it may be asymptomatic. Additionally, a close relationship between healthcare providers and patients monitoring have been shown to improve adherence by 57%.[55]

Finally, a novel antiosteoporotic agent, denosumab, has been recently added to the list of agents used for the treatment of osteoporosis and it is administered subcutaneously every 6 months. It is a human recombinant monoclonal antibody (an antireceptor activator of NF-κB ligand [RANKL] antibody) that inhibits osteoclastic-mediated bone resorption by binding to osteoblast-produced RANKL. By reducing RANKL binding to the osteoclast receptor RANK, it decreases bone resorption and turnover. This novel approach for the management of postmenopausal osteoporosis shows high adherence rate, excellent safety profile and global nonvertebral and vertebral osteoporotic fracture risk reduction.[42,56] Currently, denosumab is recommended as a treatment option for the prevention of osteoporotic fractures only in postmenopausal women at increased or high risk of fractures, risk of fracture but the patient cannot comply with the special instructions for administering oral bisphosphonates, or have an intolerance of, or contraindication to, take other osteoporosis treatments.[57,58]

Overall, improvements in treatment persistence and compliance are necessary to help reduce the risk of fractures.[35] Such measures include improved physician/patient communication and simplification of treatment regimens, close monitoring with the use of biochemical markers of response or BMD measurements, and early intervention in declining adherence, as well as a specific specialist to take responsibility for the follow-up.[52,59] Overall, after the initial management of the fragility fracture, it is crucial for the treating physician to ascertain patient's follow-up care, by providing a detailed plan highlighting the need for osteoporotic medical treatment, since long-term administration is required for effectiveness of the treatment[12] and treatment of osteoporosis at the time of a fracture represents a highly cost-effective intervention.[60]

Nutrition, Calcium & Vitamin D Supplementation, & Bone Health

Even though nutrition is only one of the several factors that influence bone mass and osteoporotic fractures, numerous nutrients and dietary components, such as calcium, vitamin D, vitamin K, phytoestrogens and nondigestible oligosaccharides can influence bone health.[61] Although the evidence base to support their role in bone health ranges from very firm to scant, depending on the nutrient/component,[61] nutritional policies for the treatment of osteoporosis should be implemented in patients with a fragility fracture. In general, maintaining optimal levels of calcium and vitamin D is fundamental for osteoporosis treatment, especially in older patients who are at increased risk for vitamin D and calcium deficiencies because of changes in dietary intake and nutrient absorption.[12]

The role and optimal level of calcium intake to compensate for skeletal calcium losses and for the treatment of osteoporosis and prevention of fractures remains unclear. The daily calcium doses for individuals older than 50 years of age vary widely from 700 to 1300 mg.[62] Recent guidelines recommend that the total daily intake of elemental calcium (through diet and supplements) for individuals over age 50 years should be 1200 mg. Regarding vitamin D, for healthy adults at low risk of vitamin D deficiency, routine supplementation with 400–1000 IU (10–25 µg) vitamin D3 daily is recommended, but for adults over age 50 years at moderate risk of vitamin D deficiency, the recommended daily dose is 800–1000 IU (20–25 µg). In general, daily doses up to 2000 IU (50 µg) are safe and do not necessitate monitoring. For patients receiving pharmacologic therapy for osteoporosis, serum levels of 25-hydroxyvitamin D should be measured after 3–4 months of adequate supplementation and should not be repeated if an optimal level (≥75 nmol/l) is achieved.[43]

Research is ongoing to investigate associations between long-term dietary intake of calcium and risk of osteoporotic fractures and to define the optimum daily calcium intake. There is controversy about the efficacy of calcium supplementation for reducing fractures[63] and the potential adverse effects of high-dose supplementation.[64] Increased calcium intake was not found to be associated with a further reduction of osteoporotic fracture rate.[62] Nevertheless, postfracture use of prescribed calcium plus vitamin D supplements alone or with antiosteoporotic drugs in females was associated with lower mortality in older people hip fracture patients.[65] Vitamin D combined with calcium was also found to be associated with statistically significant reduction in the risk of falls, and this was more prominent in patients who were vitamin D deficient.[66] The dose of oral vitamin D (cholecalciferol, ergocalciferol) that appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized persons older than 60 years of age is between 700 and 800 IU/day, whereas a dose of 400 IU/day is not sufficient for fracture prevention.[67]

Overall, for patients with a fragility fracture, the physician can prescribe calcium and vitamin D supplementation, but this should be in addition to agents that have a proven capacity to prevent fractures, such as bisphosphonates.[12] However, recent studies have shown that the role of calcium supplementation with or without vitamin D in osteoporosis management should be reassessed, as it was found to be associated with increased risk of cardiovascular events in healthy postmenopausal women, especially myocardial infarction as well as angina, stroke or even sudden death.[68,69] Therefore, this potential risk should be balanced against the likely benefits of calcium supplementation on bone and osteoporosis.

Finally, physical exercise and particularly high-intensity resistance training in postmenopausal women has a positive effect on BMD and bone health, by preventing postmenopausal bone loss.[70] Therefore, other healthcare-related professionals, such as rehabilitation professionals and dieticians can also play a role in postfracture care and particularly in the nonpharmacological management of osteoporosis including physical activity and dietary supplementation.

Assessment of Contributors to Secondary Osteoporosis & Metabolic Bone Diseases

Secondary osteoporosis can result from various chronic diseases such as rheumatoid arthritis, medications and especially long-term oral corticosteroid use, increased alcohol consumption, or nutritional deficiencies that adversely impair bone metabolism, compared with primary osteoporosis, which is associated with aging.[3,71] To improve outcome in patients presenting with a clinical osteoporotic fracture, it is important to detect and appropriately treat previously undetected contributors to secondary osteoporosis and metabolic bone diseases (SECOB). Bours et al. evaluated their prevalence in patients with a recent clinical vertebral or nonvertebral fracture, by performing BMD and laboratory investigations, including serum calcium, inorganic phosphate, 25-hydroxyvitamin D, creatinine, intact PTH, thyroid-stimulating hormone, free T(4), serum and urine protein electrophoresis, and in men also serum testosterone.[72] They found that at presentation with a fracture, 26.5% of patients had previously unknown contributors to SECOB, such as monoclonal proteinemia, renal insufficiency grade III or greater, primary or secondary hyperparathyroidism, hyperthyroidism and hypogonadism in men. Furthermore, more than 90% of patients had an inadequate vitamin D status and/or calcium intake at any level of BMD. Since these conditions are treatable or at least they require regular follow-up, systematic screening of patients with a recent osteoporotic fracture will identify those in whom potentially reversible contributors to SECOB and calcium and vitamin D deficiency are present to improve their outcome.[72]

Fall Prevention

Since a personal history of fracture is one of the strongest clinical predictors of subsequent fractures,[73] and most fragility fractures are the result of falls,[7] prevention of falls is a fundamental step to reduce the risk of recurrent fractures. Fall prevention strategies should be discussed between the patient and the primary care physician or nurse, aiming to reduce the number and severity of falls by minimizing potential risk factors for falling such as poor lighting, visual impairment and use of certain medications.[12] Interventions to reverse risk factors, such as impaired vision, should be performed when possible.[4] Continued physical therapy and exercise after discharge from the hospital can not only improve or maintain long-term level of mobility, but can also reduce fall hazards in the home by strengthening exercises and balance training.[12] External hip protectors were found to be cost effective among residents of long-term care facilities in reducing hip fractures, but not in the community because of poor compliance.[203] However, there is controversy regarding their efficacy to prevent fall injuries and therefore there is insufficient evidence to recommend for or against their routine use.[204] Nevertheless, recommendations for their use in institutionalized older people may be made on other grounds, including the large potential benefit and limited adverse effects.[204] The use of an antislip shoe device was also found to reduce the rate of falls in icy conditions.[74]

Additionally, a safe and 'fall-proof' environment should be ensured and the use of sedating or psychotropic medications should be avoided.[35,74] As there is an age-related increase in falls or an increased risk of falls in various diseases,[4] more aggressive implementation of fall prevention strategies and interventions such as pacemakers in people with carotid sinus hypersensitivity and cataract surgery should be considered.[74] Overall, recent studies have demonstrated that a thorough assessment and multifactorial interventions can reduce the rate of falls in older people living in the community[75] as well as in nursing care facilities and hospitals.[75] There is also evidence that such fall prevention strategies can be cost saving, but further research is needed to confirm the contexts in which these are effective.[74]

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