Growing in age and numbers: how can we best manage the elderly with osteoporosis?






Fânia Cristina SANTOS
MD, MSc, PhD
Osteoarticular Disease and Pain Sector, Department of Geriatrics and Gerontology
Federal University of Sao Paulo
Sao Paulo, BRAZIL

Growing in age and numbers: how can we best manage the elderly with osteoporosis?


by F. C. Santos, Brazil



The number of elderly people is fast increasing and their average age is simultaneously rising, thus the prevalence of osteoporosis is expected to grow, along with its medical and socioeconomic impact. Management of the elderly is no easy task and requires a different approach to that in younger patients. Osteoporosis therapies appear safe and efficacious in the elderly, and appropriate management of osteoporosis will reduce the associated morbidity, mortality, and economic costs. All older seniors should be educated about a bone-healthy lifestyle, which includes age-appropriate weight-bearing exercise and smoking and alcohol cessation. It is important to remember that falls play a very important role in the risk for osteoporotic fracture; thus, strategies should be implemented to reduce the occurrence of falls. The risk for vitamin D insufficiency and deficiency is high in the older senior and can contribute to falls and fractures, so deficiencies need to be treated through supplementation. Calcium intake is also important, and if inadequate, calcium supplementation is necessary. Current clinical data in older seniors have shown a benefit regarding vertebral fracture reduction with bisphosphonates (alendronate, risedronate, and zolendronic acid), denosumab, teriparatide, and strontium ranelate. However, limited data exist for some of these drugs regarding nonvertebral and hip fracture reduction. Strontium ranelate has been shown to reduce nonvertebral and hip fracture events in the high-risk elderly female population and has been found to be cost effective in preventing fractures in this population. Moreover, its antifracture efficacy is maintained over the long term.

Medicographia. 2014;36:163-169 (see French abstract on page 169)



The number of old people is growing very rapidly and is projected to more than triple globally in the next half century, from 593 million to 1.97 billion. With increasing life expectancy the prevalence of osteoporosis is expected to increase, along with its medical and socioeconomic impact.

Osteoporosis and associated fractures place significant demands on health resources— particularly hip fractures, which are a major source of morbidity and mortality among those aged over 65 years.1 Osteoporotic fractures of the hip and spine carry a mortality rate of up to 20% in one year; this is because they require hospitalization and consequently increase the risk of developing other medical complications due to chronic immobilization, such as thromboembolic disease.1 The incidence of hip fracture rises exponentially with advancing age in men and women over 75 years old.2 A review of hip fractures found that femoral neck and intertrochanteric fractures occur with approximately the same frequency in individuals between the ages of 65 and 99 years.3 Hip fractures cause acute pain and loss of function; the recovery is slow and rehabilitation is often incomplete, with many elderly people becoming permanently institutionalized in nursing homes. After a hip fracture, only half of patients return to their prefracture ability level.4

Vertebral fractures also have a major impact on a patient’s life. The SOF study (Study of Osteoporotic Fractures) assessed the effect of vertebral fractures in 7723 women aged >65 years. The impact on their quality of life was assessed according to changes in disability, pain, and fear for the future, and with every additional fracture, further deterioration in their quality of life.5 Often, vertebral fractures recur, and the consequent disability increases with increasing number of these fractures.

Fragility fractures at other sites, including the forearm, upper arm, pelvis, ribs, and clavicle, also contribute to the overall morbidity of osteoporosis.

Important issues surrounding the elderly with osteoporosis

One of the issues surrounding osteoporosis management is the diagnosis of at-risk patients before they develop a fracture; ie, identification of clinical factors that improve the detection of older adults at risk for fractures as well as disability and falls. Many elderly people at very high risk of fracture are currently not being identified.

Osteoporotic fracture risk in the geriatric patient is multifactorial, and often involves having osteoporotic bone with poor biomechanical characteristics and a higher likelihood of falls due to poorer balance, medication side effects, and difficulty maneuvering around environmental hazards.6-8 Risk factors for fracture include inherent, nonmodifiable factors, as well as those that individuals can address to prevent or slow down fracture occurrence.

It has been suggested that elderly individuals have a reduced ability to control their posture, which may predispose them to increased risk of falling.8 The risk for falls increases with advanced age,6,7 and it is estimated that 50% of senior citizens aged 85 years and older will fall at least once per year, and half of those who fall will do so more than once.8 Approximately 5% of these falls will result in a fracture.9

The senior population often has multiple comorbid conditions— such as stroke, Alzheimer’s dementia, and Parkinson’s disease—that may pose a high risk for fracture.9 Cognitive and functional changes associated with aging may make it difficult for the elderly to adhere to treatment regimens. In addition, the presence of comorbid medical conditions may be a risk factor for falls9 and thus present another barrier regarding osteoporosis care. Frailty, a common geriatric syndrome that embodies an increased vulnerability to stressors, is an independent predictor of hip fractures, hospitalization, disability, and death in the elderly and is receiving increasing attention as a risk factor for falls.10

The parallels between osteoporosis and sarcopenia are striking. Findings from a sample of oldest old women living in one community suggested a concomitant impact of severe osteopenia/ osteoporosis plus sarcopenia on frailty status.11 Sarcopenia— the age-related decline in muscle mass and function— and severe osteopenia/osteoporosis are prevalent in cases of frailty and in the prefrail elderly.11 It seems likely that sarcopenia is a substantial contributor to the increased falls and fracture risk seen with advancing age.

The use of multiple medications—which occurs very often in the elderly—particularly psychoactive medications such as benzodiazepines, antidepressants, and antipsychotics, has also been strongly associated with falls and fractures.12-14 Furthermore, the increased risk of side effects from medications in the elderly contributes to nonadherence to antifracture treatments.

Management of the elderly with osteoporosis

Osteoporosis treatment is aimed at reducing the risk of fracture, thereby reducing morbidity and mortality associated with the first fracture and preventing subsequent fractures. There is sufficient evidence to merit the treatment of osteoporosis in the elderly; however, only a small proportion of older senior citizens with osteoporosis receive treatment, particularly among those aged over 80 years.15 Moreover, many elderly individuals who start treatment do not take their treatment correctly or for long enough to lower their risk of fracture.

Management of the elderly with osteoporosis is no easy task, and requires a different approach to that in younger patients. Viable preventative and therapeutic approaches are the key to managing this problem within the aging population, and nonpharmacological and pharmacological strategies should be adopted.





Nonpharmacological strategies
Nonpharmacological strategies must be viewed as an essential part of the prevention of fractures in the elderly, but should also be employed from childhood through to adulthood. Preventive programs to address falling, as well as nutrition, hip protection, and exercise, are important nonpharmacological approaches to preventing fractures.

Interventions for falls and immobility
There are a number of different management strategies aimed at reducing the risk of falls and osteoporotic fractures in the elderly.16 All older senior citizens should be evaluated annually for falls, and strategies should be implemented to reduce the risk of falls in this population. Any patient that reports a single fall should undergo a basic evaluation of gait and balance. Questioning the individual about fear of falling is important, because not only is fear of falling a consequence of falling, but it is also a psychological risk factor for falls. Important interventions for fall prevention in the older senior citizen are outlined in Table I.16


Table I
Table I. Recommendations for fall prevention in the elderly.

Based on reference 16: Vondracek and Linnebur. Clin Interv Aging. 2009;4:
121-136. © 2009, Vondracek and Linnebur, publisher and licensee Dove Medical
Press Ltd.



Disease or disability requiring complete bed rest or severely limiting activity will cause immobility, and immobility should, wherever possible, be avoided. The reason for this is that immobilized patients may lose as much bone in a week when confined to bed as they would otherwise lose in a year. It is ideal for individuals to get some form of physical activity16 since this contributes to increased bone mass density.

Nutrition recommendations
It is necessary to ensure that elderly individuals with osteoporosis receive adequately balanced nutrition. The role of protein intake remains controversial in osteoporosis. Excessive protein intake can be responsible for a metabolic increase in acid production and acid renal excretion, with increased calciuria favoring bone loss and hip fracture.17,18 One study observed that the risk of hip fracture was not associated with calcium or vitamin D intake, but was negatively related to total protein intake (the decrease in relative risk for hip fracture paralleling the intake in animal protein).19 Another study reported that the negative effects of protein intake were related to a high ratio in the diet of dietary proteins of animal origin over vegetable proteins, which could induce a higher rate of bone loss at the femoral neck and an increased risk for hip fractures in women aged more than 65 years.20 However, this apparent deleterious effect of animal protein intake can be counteracted by dietary or supplemental calcium and vitamin D (500 mg as calcium citrate malate and 700 IU vitamin D per day).21 Inadequate dietary protein intake in the presence of adequate total calcium intake does not seem to confer any protection against fractures.22

Adequate intake of calcium is important. Encouraging consumption of foods rich in calcium is one of the best ways to preserve body calcium economy, and when dairy consumption is low, a calcium supplement should be considered. Additionally, adequate intake of vitamin D should be recommended.23 However, hypovitaminosis D principally results from insufficient skin exposure to sunlight and the reduced efficacy of vitamin D synthesis in the skin of elderly individuals. Low sun exposure in the elderly is related to an indoors style of living and/or wearing clothing that leaves little skin exposed. If there is inadequate sun exposure as well as a diet with inadequate levels of vitamin D, supplements of this vitamin may need to be taken.23 Vitamin D also plays an important role in falls,24 in addition to bone strength.

Exercise
A systematic review found that in individuals with an increased risk of fracture, bone strength was improved by weight-bearing aerobic exercise with or without muscle strengthening exercise when the duration of the intervention was at least 1 year.25 Programs of resistance exercise for the elderly need to be evaluated carefully. Strength-training programs and the intensity of the training should be carefully planned and progressively adapted to suit the body.

The major benefit of exercise in patients with osteoporosis may be an improvement in muscle strength and coordination, which, in turn, decreases the frequency of falls.26 Exercise interventions have mainly been reported to reduce risk factors for fracture; ie, produce a decrease in the propensity to fall and/ or an increase in bone mass density. A Cochrane meta-analysis showed that multifactorial interventions and single, supervised exercise interventions can both reduce the risk of falling, with multifactorial interventions also reducing the rate of falls (relative risk [RR], 0.69; 95% confidence interval [CI], 0.49-0.96).27 The general recommendation is that exercise should be performed two to three times per week and must include 15 to 60 minutes of aerobic exercise and a set of strength training. Exercise intensity should be at 70% to 80% of functional capacity or maximum strength.26

Smoking and alcohol cessation
Current smoking and excessive alcohol consumption are associated with an increased risk of fracture,23 and smoking cessation and reduction in alcohol consumption can slow the rate of bone loss. Despite a lack of data in older seniors and the fact that the benefits of smoking cessation for osteoporosis may be delayed, the other health benefits of smoking cessation make it important for all older seniors.26 Alcohol may interfere with bone metabolism through direct toxic effects on osteoblasts, as well as indirectly through adverse skeletal effects caused by nutritional deficiencies in calcium, vitamin D, and proteins, which are prevalent in heavy drinkers.26

Hip protectors
Use of external hip protectors is aimed at reducing the impact of falls onto the hip. A meta-analysis of randomized controlled trials demonstrated no benefit from hip protectors in community-dwelling seniors.28 By contrast, a pooled analysis suggested that two-sided devices may potentially reduce the risk of hip fracture, at least in institutionalized elderly individuals.29 Although the available evidence is insufficient to allow firm and final conclusions or recommendations, it would seem that it may not be appropriate to discount the potential benefit of this intervention in a long-term care setting. Poor compliance is the main drawback with these devices, as patients tend to find them uncomfortable and cosmetically unappealing.

Pharmacological strategies
In all older seniors a diagnosis of osteoporosis will in theory warrant drug therapy. However, several factors need to be taken into consideration before instituting drug therapy for the management of osteoporosis in the elderly population to determine whether there is evidence to support a benefit of osteoporosis therapy.

Vitamin D and calcium supplementation
The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)30 provides clinical practice recommendations to ensure the optimal management of elderly and postmenopausal women with regard to vitamin D supplementation: patients with serum 25-hydroxyvitamin D (25[OH]D) levels of <50 nmol/L have increased bone turnover, bone loss, and possibly mineralization defects compared with patients with 25[OH]D levels of >50 nmol/L. Similar relationships have been reported for frailty, nonvertebral and hip fracture, and all-cause mortality, with poorer outcomes among those with 25[OH]D levels at <50 nmol/L. Thus, the ESCEO recommends that 50 nmol/L (ie, 20 ng/mL) should be the minimum serum 25(OH)D concentration at the population level and in patients with osteoporosis to ensure optimal bone health. Below this threshold, vitamin D supplementation is recommended at 800 to 1000 IU/day. The ESCEO recommends that fragile elderly subjects should have a minimum serum 25(OH)D concentration of 75 nmol/L (ie, 30 ng/ mL) for the greatest impact on fracture risk reduction.30

A meta-analysis of calcium and calcium/vitamin D supplementation concluded that oral vitamin D appears to reduce the risk of hip fractures, but only when it is combined with calcium supplementation.31 In this meta-analysis, calcium/vitamin D supplements (1200 mg of calcium and 800 UI of vitamin D/day) significantly reduced fracture risk by 12%, and they also reduced bone loss (by 0.54% at the hip and 1.19% in the spine). In a subgroup analysis based on age, fracture risk reduction was 11% in those aged 70 to 79 years and 24% in those aged 80 years, while in those aged 50 to 69 years it was 3%.

Moreover, among older individuals, vitamin D supplementation has been found to reduce the risk of falling by 19%, and to a similar degree as active forms of vitamin D (700-1000 IU/ day).24

There have been suggestions that calcium supplementation, either as monotherapy or combined with vitamin D, increases cardiovascular risk. However, the trials that have reported this were not valid in the sense that they were not primarily designed to assess cardiovascular events. When it is necessary to supplement calcium intake, either calcium carbonate or calcium citrate can be used.16 The calcium citrate form may be advantageous for older seniors, since calcium citrate absorption does not rely on gastric acid (unlike calcium carbonate), and older seniors may suffer from achlorhydria. Moreover, patients taking proton pump inhibitors may benefit more from supplementation with calcium citrate.16

Bisphosphonates
Data from one clinical trial showed that in a subgroup of women aged 75 years or above, alendronate reduced the risk of new vertebral fractures by 38% during an average follow-up of 2.9 years.32 The absolute risk reduction with alendronate for combined clinical hip, spine, and wrist fractures was greatest in the 75- to 85-year age group: there were 65, 80, 111, and 161 women with fractures per 10 000 person-years in the age groups 55 to <65 years, 65 to <70 years, 70 to <75 years, and 75 to 85 years, respectively.33 For risedronate, a 44% reduction was observed in the riskof vertebral fractures in women aged 80 years or above, but there was no significant difference in the incidence of nonvertebral fractures.34 In a post hoc analysis of the HIP study (Hip Intervention Program), risedronate significantly reduced the risk of hip fracture by 46% in women aged up to 100 years with established osteoporosis.35 A study with zoledronic acid taken intravenously once a year demonstrated the efficacy of the treatment in reducing the risk of hip fracture in older postmenopausal women aged 65 to 89 years.36 Over 3 years, hip fracture incidence was significantly reduced by 41%. In a post hoc subgroup analysis of pooled data from the HORIZON trials (Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly), which assessed the effect of zoledronic acid treatment in postmenopausal women aged 75 years and older, significant reductions were observed in the risk of any clinical fracture (35%), clinical vertebral fractures (66%), and nonvertebral fractures (27%).37 Common adverse events were flu-like symptoms.

Denosumab
In a post-hoc analysis of the 3-year FREEDOM trial (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months), in the subgroup of postmenopausal women aged 75 years or above, denosumab treatment reduced the relative risk of new vertebral and hip fractures by 69% and 47%, respectively.38 There was a possible increased rate of eczema and cellulitis.

Raloxifene
Although older women have been included in some studies of raloxifene, the numbers have been small and there are no published data on older cohorts or subgroups.

Strontium ranelate
Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. Pooled data on strontium ranelate from the trials SOTI (Spinal Osteoporosis Therapeutic Intervention; mean patient age, 70 years [range 50 to 96 years]) and TROPOS (TReatment Of Peripheral Osteoporosis Study; mean patient age, 77 years [range 70 to 100 years]) revealed risk reductions after 3 years of 32%, 31%, and 22% for vertebral, nonvertebral, and any clinical fracture, respectively, in the subgroup of women aged 80 years or above with osteoporosis.39 Strontium ranelate is the only antiosteoporotic drug to have been shown to achieve an early and sustained reduction (up to 5 years) in the risk of vertebral and nonvertebral fracture in such an elderly population (aged ≥80 years).40 Additionally, in patients with a mean age of 72 years, vertebral and nonvertebral fracture incidence was lower over a period of 5 to 10 years than in a matched placebo group, thus showing that the anti-fracture efficacy of strontium ranelate is maintained over the long term.41

In TROPOS, strontium ranelate significantly reduced the risk of hip fracture by 36% in a high-risk subgroup (those aged ≥74 years with a femoral neck bone mineral density T-score of ≤–3, corresponding to a T-score of –2.4 when using data from NHANES III [the Third National Health and Nutrition Examination Survey] as a reference).42

With regard to cost effectiveness, a recent meta-analysis of trials undertaken in different settings (Belgium, the UK, and Sweden) confirmed that treatment with strontium ranelate is cost-saving in women with osteoporosis aged 80 years and older.43 Furthermore, for all ages, the cost per quality-adjusted life year gained with strontium ranelate compared with no treatment, when assuming adherence similar to bisphosphonate therapy, was less than the cutoffs established in countries like the UK and Sweden. In patients at risk of venous thromboembolism, strontium ranelate should be used with caution and discontinued in the event of an illness or a condition leading to immobilization.44 Patients with significant risk factors for cardiovascular events should only be treated with strontium ranelate after careful consideration.


Table III
Table II. Pharmacological therapy for osteoporosis in the elderly.

Abbreviations: ACF, any clinical fracture; GI, gastrointestinal; HF, hip fracture; MI, myocardial infarction; NVF, nonvertebral fracture; VF, new morphometric vertebral fracture; VTE, venous thromboembolism; WF, wrist fracture.



Teriparatide
Teriparatide is an option for patients who are at high risk of fracture or who cannot tolerate, or fail on, other therapies. Daily administration by injection in the older senior can be challenging. A study of the clinical fracture incidence, back pain, and health-related quality of life in patients receiving teriparatide treatment over a period of 18 months and in the 18 months following treatment reported a reduced clinical fracture incidence in the subgroup of 589 postmenopausal women with osteoporosis who were aged ≥75 years.45 In addition, an improvement in quality of life was observed, and possibly also an early and significant reduction in back pain, which lasted for at least 18 months after teriparatide discontinuation when patients were taking other osteoporosis medication.

Table II (page 167) summarizes data on the current pharmacological agents available for the treatment of osteoporosis in the elderly.

Finally, there is limited data on the clinical efficacy and safety of specific antiosteoporotic treatments for the reduction of fracture risk in the elderly with osteoporosis, particularly in the elderly aged ≥ 75 years.46 Given the positive impact of medications on fracture prevention, the low risk of drug-drug interactions, and low incidence of adverse effects, prescription of antiosteoporotic drugs should not be considered “inappropriate” in older patients. However, it is necessary to adopt different strategies in this patient age group, as their fracture risks and treatment strategies may be quite different from younger populations. Extending strategies for fracture risk reduction beyond osteoporosis, targeting several clinical conditions rather than focusing on a single condition, may be preferable. Strategies focused on a combination of clinical conditions would be interesting in the elderly; for example, osteoporosis and sarcopenia or sarcopenic obesity, which has very recently been termed “dysmobility syndrome” and is characterized by difficult or impaired mobility that leads to an increased risk of adverse musculoskeletal outcomes such as falls and fractures.47

Conclusion

It is important for health care providers to be fully aware of the potential risks and benefits of treating osteoporosis in the elderly, a high-risk group for osteoporotic fracture as well as for osteoporosis-related complications and treatment-related adverse events. Osteoporotic therapies appear safe and efficacious in the elderly population, and appropriate management would reduce the morbidity, mortality, and economic costs associated with this disease. The best management of the elderly population with osteoporosis includes exercise training, optimal dietary calcium intake, vitamin D supplementation, and use of antiosteoporotic drugs. There is good evidence for the benefits of bisphosphonates (alendronate, risedronate, and zolendronic acid), denosumab, teriparatide, and strontium ranelate in vertebral fracture reduction, but there are limited data regarding the reduction of nonvertebral and hip fracture for some of these drugs. Strontium ranelate has demonstrated an ability to reduce nonvertebral and hip fracture events in the high-risk elderly female population. Furthermore, its cost effectiveness has also been shown for fracture prevention in this population, as well as its maintained antifracture efficacy over the long term.

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Keywords: antiosteoporotic treatment; elderly; fracture prevention; osteoporosis