Osteoporosis is increasing due to the aging of the population. Women with cognitive impairment from childhood are at disproportionally high risk for osteoporosis and fractures. Suggested explanations for this increased risk include high use of anticonvulsant medications, lower peak bone densities, and higher rates of nonambulation. Down syndrome seems to be an independent risk factor for low bone density and fractures, presumably due to lower muscle tone. Here, the limited information available on the epidemiology of osteoporosis in the general population and in women with cognitive disabilities is briefly reviewed. Health care professionals should consider women with cognitive disabilities at high risk for osteoporosis and fractures. Studies are needed to determine screening regimens and prevention strategies appropriate for women in this population.
Osteoporosis is not a new disease (Cooke, 1955), but it is becoming more prevalent due to the aging of our population (Boyle et al. 2001). This condition includes low bone density along with microarchitectural distortion of bone that predisposes to fractures (National Institutes of Health Consensus Development Panel, 2001; World Health Organization, 1994). Osteoporosis itself is a silent disease. The major clinical consequence of this disease is fracture. Hip fractures due to osteoporosis have devastating consequences, with tremendous mortality and morbidity. About a quarter of all patients over 50 years of age with a hip fracture will die within one year. At 6 months after a hip fracture, only 15% of people can walk across the room without help (National Osteoporosis Foundation, 2005). Other types of fractures due to osteoporosis can also cause chronic pain and further impair mobility.
Women with cognitive impairment since childhood (e.g., mental retardation, developmental disabilities, Down syndrome) are at high risk for osteoporosis and fracture. In this paper I briefly review the epidemiology of osteoporosis in the general population and then review the available literature on osteoporosis, low bone density, and fractures in women with cognitive impairment.
Epidemiology of Osteoporosis in the General Population
Bone is built in early childhood through puberty and adolescence. Peak bone mass is attained between ages 18 to 20 (Eisman, 1993; Seenan & Tsalamandris, 1993). The level of peak bone mass is determined by many factors, including genetics, diet, hormones, and environmental factors (Soyka, 2000). Bone mass remains constant until approximately ages 30 to 35 after which a slow decrease in bone density commences in both genders. This slow bone loss remains constant in men, whereas women experience a sudden, rapid decline in bone mass on top of the slow loss after menopause that continues for 5 to 7 years. Women can lose up to 20% of their total bone mass during this time (Wehren, 2003). The prevalence of osteoporosis increases as women age due to the physiologic decreases in bone mass (Looker et al., 1995). It is estimated that postmenopausal Caucasian women have close to a 50% chance of experiencing an osteoporosis-related fracture in their lifetime (Ulom-Minnich, 1999). Most fractures do not happen until a woman is in her 70s and 80s, however, which underscores the importance of prevention in earlier life.
Osteoporosis occurs in both genders, but women comprise 75% to 80% of all osteoporosis related hip fractures in the United States (Ulom-Minnich, 1999). Women have lower peak bone densities than do men due to a combination of less muscle mass and genetics. Then, women experience a temporary rapid decline in bone mass after menopause, which men do not. Consequently, women have lower bone density (and subsequent higher fracture rates) at all ages (Melton, 2003).
Most of the clinical recommendations about osteoporosis are based on research in Caucasian women. African American women tend to have higher bone densities than do Caucasian women (Wehren, 2003). Asian American women and women from Asia have, on average, lower bone densities than do Caucasian women (Garn, Pao, & Rihl, 1964; Wehren, 2003). Caucasian women over 65 have twice the fracture risk as age-matched African American women (National Osteoporosis Foundation, 2005). Hispanic women's risk is intermediate between Caucasian and Asian women and African American women (National Osteoporosis Foundation, 2005).
Bone Mineral Density
Bone mineral density (BMD) is a surrogate marker for bone strength, an important marker for fracture risk. According to the World Health Organization (1994) diagnostic criteria, a BMD of 1 to 2 standard deviations (SDs) below the reference criteria (bone density of a 35-year-old Caucasian woman) is defined as osteopenia, and more than 2.5 SDs below the reference is classified as osteoporosis (World Health Organization, 1994). National Health and Nutrition Examination Survey (NHANES) III data clearly demonstrate that fracture risk increases with decreasing BMD levels (Looker et al., 1995).
Women With Cognitive Impairment
Few researcher have examined osteoporosis and fractures in women with cognitive disabilities (see Table 1). In all of the available studies, investigators have found an increased prevalence of osteoporosis in this population. The reason for the high prevalence of osteoporosis in women with cognitive impairment is unclear. Risk factors include the use of anticonvulsant medication, diagnosis of Down syndrome, age, and ambulatory status. Bone mineral density is controversial in this population as a predictor of fracture, though the data are sparse. The majority of studies reviewed here included both males and females, and many of the researchers did not stratify results based on gender. The following review is a compilation of results, with specific information on women when available.
The trend toward deinstitutionalization of adults with cognitive impairment in the United States has flourished since the 1970s (Lakin, Anderson, Prouty, & Polister, 1999). As such, the health care system is now responsible for the majority of adults with cognitive impairment. This population is aging along with the general population. The American Association on Mental Retardation estimates that there are over 500,000 people with developmental disabilities aged 60 years or older. That number is predicted to double by 2030, reflecting the aging of our entire population (Hammel & Nochajski, 2000). Fractures in people with cognitive impairment present a very difficult clinical management dilemma. Many patients do not have the verbal abilities to inform their caretakers that they have pain and, similarly, do not understand the rationale for immobilization or medication. Therefore, it is important to understand the epidemiology of osteoporosis and fractures in this population in order to begin to develop prevention recommendations.
Anticonvulsant Medication Use
Anticonvulsant medication is used to control seizures well as limit aggressive or agitated behavior. The increasing use of anticonvulsant medications for behavior management may contribute to the high osteoporosis rates in women with cognitive impairment. Anticonvulsant medication has been directly linked to low bone density and osteoporosis. Anticonvulsant medications such as phenytoin, carbamazepine, and valproic acid can alter Vitamin D metabolism (Sato et al., 2001; Sheth et al., 1995). Phenytoin and carbamazepine are also direct toxins to osteoblasts (Feldcamp, 2000). Newer anticonvulsant medications, such as topiramate, gabapentin, and lamotrigine, may still cause lower bone density, though less so than the older medications (Farhat et al., 2002). In a study of 273 adults with developmental disorders, Ray, Papaioannou, Ioannidis, and Adachi (2002) found that 40% were taking at least one anticonvulsant medication. Bone density was correlated with ingestion of anticonvulsant medications, with those people who were taking more than one type of anticonvulsant having the lowest bone density. In addition, many people with cognitive disabilities also have concomitant seizure disorders (Lohiya et al., 1999) and may be at higher risk of traumatic fracture during a seizure.
Ryder (2003) used a case-control methodology to compare 23 adults with developmental disabilities residing in a state-run inpatient facility who had fractures to 23 age-, race-, and gender-matched controls. The results demonstrated a nonsignificant trend for a relationship between anticonvulsant medication use and fracture. Overall, 83% of the cases and 52% of the controls were taking at least one anticonvulsant medication.
In a cross-sectional study of inpatients at a different facility for individuals with severe disabilities, Kawada (2002) found a significant relationship between use of valproate and fracture. In this study, 51% of the population was taking valproate; 30%, phenytoin; 40%, carbamazepine; and 27%, phenobarbital. No data were presented on how many people were taking multiple anticonvulsant medications. Kawada did not find a significant relationship between history of anticonvulsant medication or duration of medication use with bone density evaluation.
Down syndrome may be an independent predictor of low bone mass and risk of fracture. Down syndrome is the most common specified genetic cause of developmental disabilities and is often associated with musculoskeletal disorders. Specifically, many individuals with Down syndrome have motor clumsiness that is attributed to hypotonia and joint hypermobility. Initial bone growth is slow and the development of bone maturation may be delayed in the first 8 years of life (Angelopoulou, Tsimaras et al., 1999) There is evidence that children with Down syndrome achieve much lower peak bone densities than do typical age-matched controls and that low bone density persists into adulthood (Grimwood, Jynarm Bickerstaff, & Suvarna, 2000; Kao, Chen, Wang, & Yeh, 1992). Many children with Down syndrome are delayed in walking, which might be a cause of low peak bone density. There is also some evidence that this population has lower muscle strength compared to individuals with other etiologies of mental retardation, which could also contribute to lower bone density (Angelopoulou, Tsimaras et al., 1999). Hypotonia, decreased muscle strength, and lower peak bone densities may partially explain the significant increases in low bone density and fracture rates among patients with Down syndrome in adulthood (Angelopoulou, Souftas et al., 1999; Sepulveda et al., 1995).
In two small, case control studies, Sepulveda et al. (1995) and Angelopoulou, Souftas et al. (1999) compared community-based women with Down syndrome to age-matched controls. Sepulveda et al. compared 15 adults (4 women) with 25 age-, weight-, and gender-matched control subjects (13 women) who were recruited from an obesity research center. All of the women with Down syndrome had lower BMD. The authors estimated that Down syndrome accounted for 32% of the variance in BMD. Angelopoulou, Souftas et al. also compared adults with Down syndrome (13 women) to controls (15 women). All of the adults with Down syndrome had lower BMD than did the age- and gender-matched controls. Interestingly, the males with Down syndrome had even lower BMD than did the females. Tyler, Snyder, and Zyzanski (2000) found Down syndrome to be independently correlated with low bone density and osteoporosis in a study of community-based women screened at a community center for adults with developmental disabilities. More recently, Baptista, Varela, and Sardinha (2005) measured bone density as well as bone mineral content and indices of femoral bone strength in 33 women with Down syndrome and 33 healthy controls. The women with Down syndrome had lower BMD, bone mineral content, and strength indices. There have been no studies in which researchers have compared women with Down syndrome matched in age to women with other types of cognitive impairment, however.
There is reason to suspect that women with other genetic entities that cause mental retardation may be related to osteoporosis as well. In a study performed in Poland, Pluskiewicz et al. (2003) measured bone density of the hand phalanges using quantitative ultrasound in 50 children with various genetic disorders (e.g., Down syndrome, Martin-Bell syndrome, Marfan-Mass phenotype). They reported a significantly lower bone density in all of the patients compared to controls without genetic disorders.
Although the life expectancy of adult women with Down syndrome is lower than it is for those in the general population (67 years for those with no Down syndrome; 57 for those with Down syndrome), improved medical care has greatly increased the number of years a woman with cognitive impairment can expect to live (Brown, 2004). There is some evidence that women with Down syndrome may go through menopause earlier than do average women, which may add to their osteoporosis risk and predispose them to fractures at younger ages (Brown, 2004). Increasing age is a clear risk factor for low bone density, osteoporosis, and fracture in this population (Kawada, 2002; Lohiya et al., 1999). Although minimal data are available, it appears that fractures in women with cognitive disabilities occur at earlier ages than osteoporosis fractures in postmenopausal women without disabilities (Schrager, Gettings, & Kloss, 2006). In a chart review study I performed in 2004, 33% of women over 18 in a population with diagnoses of either Down syndrome, mental retardation, or developmental disabilities had a history of a fracture. The majority of these fractures occurred when women were in their 40s and 50s, much earlier than would be expected.
Inactivity is a major risk factor for osteoporosis. Bones need continued muscular strain to maintain their strength and to continue the normal remodeling process. The net result of disuse is thinning of cortical bone and subsequent increased fracture risk (Takata & Yasui, 2001). Studies of women in the first 6 months after a spinal cord injury have shown rapid bone losses of up to 50% in their lower extremities (Ott, 2001). Some adults with severe cognitive impairment are nonambulatory. Many of the most severely impaired people have remained institutionalized (Lakin et al., 1999). In studies of institutionalized adults with both intellectual disability and mobility disorders, researchers have found profound osteoporosis and low bone density (Mugica et al., 2002; Wagemans, Fiolet, van der Linde, & Menheere, 1998). Institutionalized adults may be different than adults in the general population due to possible lower activity levels and decreased exposure to sunlight.
Even though bone density is lower in people who are nonambulatory, fracture rates may not be a factor in this difference. Kawada (2002) stratified their population by ambulatory status (Grade 1, lying in bed; Grade 2, able to sit for reasonable lengths of time; Grade 3, not able to walk, but able to move without assistance; and Grade 4, able to walk) and found no significant difference in fracture risk. Lohiya et al. (1999) actually found higher fracture rates among those adults who were able to ambulate independently. As is seen in the elderly population as well, if people are independent, they are at higher risk of falling. Adults with cognitive disabilities seem to have different risk factors for falling than does the elderly population without disabilities (Hsieh, Heller, & Miller, 2001). Therefore, nonambulatory adults may suffer from nontraumatic fractures, such as vertebral compression fractures, as opposed to hip fractures in those who are ambulatory (Wagemans et al., 1998).
Bone Mineral Density
In the general population of postmenopausal Caucasian women, bone density is clearly linked to fracture risk. Every SD drop in bone density predicts double the fracture risk (Wehren, 2003). In a population of women with cognitive disabilities, the relationship is not as clear. Although some researchers have found a relationship between lower bone densities and increased fracture risk (Aspray, 1998; Kawada, 2002), others have not (Ryder, 2003). In all of the studies reviewed in Table 1, the women with cognitive disabilities had lower bone densities compared to either matched control subjects or to population data as a whole. A large, population-based study should be performed to determine prevalence of low bone density and osteoporosis and their relationship to fracture risk in this population of women with broad ranges of cognitive impairment.
Osteoporosis and fractures are very common among adult women with cognitive disabilities. The risk factors do not appear to be the same as in the general population of postmenopausal Caucasian women. Anticonvulsant therapy and ambulatory status are major contributors to low BMD, osteoporosis, and fracture in this population. In many of the existing studies, investigators had very small samples and used differing measurements of BMD. Further research needs to be done to elucidate specific risk factors for osteoporosis and fracture in this population. The health care profession should consider women with Down syndrome or developmental disabilities of any type as very high risk for osteoporosis and focus on early screening, early diagnosis, and ongoing prevention activities.
Author: Sarina Schrager, MD, University of Wisconsin, Department of Family Medicine, 777 S. Mills St., Madison, WI 53715. firstname.lastname@example.org