BoneKEy-Osteovision | Commentary
Options for osteoporosis treatment in the elderly
DOI:10.1138/2001040
Osteoporosis is a major clinical problem in older women and men. Almost any bone can fracture as a result of the increased bone fragility of osteoporosis. Such fractures are associated with high health care costs, loss of quality of life and increased mortality with all “major” fracture types, i.e. excluding peripheral fractures such as hands and feet. As the relative (and absolute) incidence of osteoporotic fractures, including particularly hip fractures, increase with advancing age, the greatest costs in terms of health care expenditure and loss of quality of life tend to occur in the elderly. However few studies have been performed involving older subjects of 80+ years.
Villareal et al. () describe a potentially key study in older women (older than 75 years; mean age 82 years) who were randomized to treatment with estrogen plus cyclical medroxyprogesterone acetate or placebo on a 2:1 basis and followed with bone density over a 9-month period. In all subjects diet was assessed and if necessary, supplemented to achieve intakes of calcium of 1200 mg/day and vitamin D of approximately 800 IU/day. They observed a bone density response difference compared with placebo subjects of 1.4 to 3.9% varying between skeletal sites and even a difference of 1.1% in total body BMD. They noted that the “effect” was greater when analyzed on a per protocol basis, which may reflect the difficulty some participants had in adhering to the protocol. Nevertheless the relative bone density increase, somewhat surprisingly, is comparable to the “best” results observed in younger women. The importance of this study is that few comparable studies have been carried out in older-old women. Of course with such a small sample size, there were no data on fracture rates. Given that studies show variable correlations between changes in bone density and fracture rates, this is a serious deficiency in this arena of patient care.
An aspect of the study, as noted above, that was also interesting was the high proportion of women randomized to HRT, who withdrew or did not complete the trial according to protocol, i.e. 18 of 45 (40%) compared with 4 of 22 (18%) in the placebo arm. This high drop-out rate was even after study selection criteria and patient choice had narrowed the study group to just 22% of the initial group of “eligible” patients that had been screened. Taken together with the drop-out rate, these proportions suggest that HRT may be tolerated and effective but perhaps only in 10% of older women.
This study is all the more important in view of the recent Risedronate study () in which a large subset of older women (aged 80 yr and over) was selected on the basis of falls risk and not on bone density criteria.. In this older subset of women there was only an 18% and non-significant reduction in fracture rates, compared with the significant (41%) reduction in hip fracture rates in the ‘younger’ (aged 70 - 79 yr) women. This paper attracted considerable discussion (). At one level, this “lack” of benefit could simply be explained by the women not being osteoporotic, thus treatment of osteoporosis was not likely to be efficacious. However, as bone density data were not available in most of these older women, this paper does leave uncertainties about the efficacy of anti-resorptive therapy in older women (and perhaps men). Some older women have been included in other studies but no study has focused on these older age groups, except with vitamin D and calcium (see below).
There is a large body of evidence for vitamin D deficiency in older institutionalized and even community-dwelling men and women (,,,,,). In the face of this evidence that calcium and vitamin D are beneficial in younger elderly women (), the concept of vitamin D supplementation or replacement seems both rational and reasonable. This approach is also supported by studies with both vitamin D and calcium in older women (and men) that have shown improvements in muscle strength and, more importantly, reduction in fractures, including hip fractures (). In the community living elderly there is less evidence and less rationale for such an approach (). However, there is little ground for concern regarding risk from simple vitamin D and calcium supplementation in all elderly individuals (). Any benefit may arise as much from reduced proximal muscle weakness (from osteomalacia) as from any major effects of reversing adverse effects of secondary hyperparathyroidism on bone (). The simplest approach may be a single large oral dose (250,000 to 300,000 units) once per year in the latter part of autumn/fall.
In summary the study of Villareal et al. indicates that older women can benefit, in terms of bone density increase, from oral hormone replacement therapy. However, there may be only a small proportion of older women in whom it is tolerated. Simple vitamin D and calcium supplementation should be considered as a baseline in all older women and men and particularly in all institutionalized elderly. There is no clear evidence that the potent bisphosphonates do not “work” if they are selected on the basis of low bone density. However, it remains to be shown whether older women (or men) will benefit in terms of bone density improvement and most importantly in terms of fracture reduction with these agents. As medicine works towards a stronger evidence base, dilemmas constantly arise regarding those groups of individuals not included in the studies that have demonstrated efficacy of new agents. The study of Villareal indicates that it is possible to fill in some of these gaps for older-old individuals by performing such studies albeit with surrogate end-points.
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