Premature Graying, Balding, and Low Bone Mineral Density in Older Women and Men: The Rancho Bernardo Study

Introduction

Premature graying and/or balding hair have been proposed as potential markers for the identification of persons at risk for osteoporosis. Results from previous studies examining the utility of prematurely gray hair (defined as almost all hair gray by age 40) as a risk marker for a variety of chronic conditions have been inconsistent: Orr-Walker and colleagues (1997)reported in women, and Rosen et al. (1994)reported in both women and men, a positive association between prematurely gray hair and low bone mineral density (BMD), but Beardsworth et al. (1999)failed to find any association with BMD in women.

Balding is another observable potential marker of those at risk of many hormone-mediated conditions including osteoporosis. No published studies have reported the relation between balding and low BMD.

In the present study we examine the association of premature graying or balding with bone mineral density in a community-based sample of older men and women.

Methods

Results

The 1,207 participants (490 men and 717 women) in the 1992-96 clinic visit ranged in age from 50 to 98 years with a mean age of 70.7 (sd = 10.1) for men and 71.6 (sd = 10.9) years for women. All participants who attended the 1992-1996 clinic visit provided information on premature graying. The 380 men and 518 women who had provided information on balding status 10 years earlier were similar in age at the clinic visit, with a mean of 70 years (sd = 10.4) for men and 70.4 (sd = 11.4) years for women. Overall, 10.8% of the men and 9.9% of the women reported premature graying, and 51.1% of the men and 9.5% of the women reported balding. Among the women, 47% were current estrogen users.

Among both men and women, there were no significant differences in mean age between those who were versus those who were not prematurely gray (p> 0.10) (Table 1). However, as compared to those who were not prematurely gray, a significantly greater proportion of the prematurely graying men and women were currently less than 60 years of age (13.7% vs. 26.4% for men, and 13.8% vs. 38.0 % for women, p’s < 0.001). Conversely, a significantly lower proportion of men and women over 80 years old reported being prematurely gray (p’s <0.001). Additionally, a greater proportion of prematurely gray women reported current estrogen use as compared to those who were not prematurely gray (57.1% vs. 45.9% respectively, p= 0.07).

Men and women who were balding did not differ significantly in mean age from those who were not balding (p> 0.10). However, a significantly greater proportion of men and women who were not balding were currently less than age 60 as compared to those who were balding (22.0% vs. 12.9% for men and 21.1% vs. 4.2% for women, p’s < 0.001). As compared to those who were not balding, a significantly greater proportion of balding women used glucocorticosteroids and estrogen replacement (0.4% vs. 4.1%, p < 0.01, and 50.7% vs. 68.8%, p=0.017, respectively). Among both men and women, there were no significant differences (p’s > 0.10) by premature graying or balding status in alcohol use, smoking, exercise, and use of calcium supplements, diuretics, thyroid medication use, or in men, use of glucocorticosteroids.

After adjusting for age, body mass index (BMI), smoking, exercise, and use of alcohol, calcium supplements, diuretics, glucocorticosteroids, thyroid medications and, in women only, estrogen use, mean BMD levels at all four sites (femoral neck, hip, spine, and total body) did not differ by premature graying in either men or women (Table 2). Using the same model, men who were not balding had a five percent higher mean total body bone density compared to balding men (1.149 g/cm² vs. 1.095 g/cm², p < 0.05). The opposite was true for women, but the differences were observed at the femoral neck and total hip. Balding women had a 23% significantly higher mean BMD at the femoral neck and a 24% significantly higher total hip BMD than women who were not balding (femoral neck = 0.915 g/cm² vs. 0.740 g/cm² and total hip = 1.043g/cm² vs. 0.837 g/cm² respectively, p < 0.05).

Age and sex-specific analyses of variance with participants stratified into front, back, and all-over-head balding categories revealed no significant differences (p’s > 0.10) in mean BMD between categories at any of the four BMD sites. In men, those reporting balding onset by decade were normally distributed across the age categories; none reported balding before age 20, 8% during their 20’s, 14% during their 30’s, 28% during their 40’s, 26% during their 50’s, 15% during their 60’s, 6% during their 70’s, and 2% during their 80’s. In women, those reporting balding onset by decade were similarly distributed; none reported balding before age 20, 2% during their 20’s, none during their 30’s, 9% during their 40’s, 11% during their 50’s, 37% during their 60’s, 34% during their 70’s, and 6% during their 80’s. When stratified by decade of onset of balding, there were also no differences in BMD (data not shown).

Discussion

The results of the present study do not support the thesis that premature graying is a marker for low BMD. At all sites, there were no significant differences in BMD between those who were and were not prematurely gray.

Among men, balding was associated with a five percent difference in mean total body BMD. However, measurement of total body BMD is not considered to be a definitive measure of BMD, and is used more frequently only as a confirmation of findings at the spine and total hip (Fogelman & Blake, 2000). The association of higher BMD levels observed at the total body site in non-balding men may be simply due to the confounding mixture of cortical and trabecular bone included in the total body bone density measurement itself. In this sample of men, balding was unrelated to BMD at the femoral neck, total hip, and lumbar spine. It is unlikely these results were due to recall bias and subsequent misclassification. A recent study by Taylor and colleagues (2004)has shown that self-report of balding in men, whether current or retrospective, is adequate when compared with a trained observer’s assessment.

In contrast, significant differences in BMD in women between those who were and were not balding were observed at the femoral neck and total hip. These differences may be partially explained by the higher rates of glucocorticosteroid and estrogen use among the balding women. Glucocorticosteroids are associated with balding (Juricskay & Telegdy, 2000), and estrogen replacement therapy is associated with increased bone density (Morton et al., 1998). However, these differences remained significant after adjustment for these particular covariates.

The lack of association between premature graying and BMD is in accord withBeardsworth and colleagues (1999), who examined BMD at the lumbar spine and femoral neck in a small group of 52 prematurely gray-haired East Yorkshire women as compared to a sample of age- matched women who were not prematurely gray. However, Beardsworth and colleagues (1999)studied participants much younger than Rancho Bernardo women (mean age=52.8) and included pre-menopausal women (n=20), who are known to have relatively stable and higher BMD levels when compared with older, postmenopausal women.

Results of the present study are in contrast with those of two smaller studies that reported a positive association between premature graying and low BMD (Orr-Walker et al., 1997;Rosen et al., 1994).Orr-Walker (1997), using the same definition as the present study, found significant associations of premature graying with low BMD at the femoral neck, trochanter, and total body in a sample of 293 healthy postmenopausal women. However, “premature graying” explained only 0.6 to 1.3% of the variance in BMD, which the authors attributed to the infrequency of premature graying in this population. Rosen and colleagues (1994)compared 36 men and women with osteopenia and 27 men and women without osteopenia and found a positive association between premature graying and low BMD at the lumbar spine. However, this small sample was recruited from a metabolic bone clinic (lumbar BMD t-score, below –1.0).

Premature graying of the hair is associated with various disorders of the endocrine system. The actual pathophysiology of melanin depletion in hair follicles is unknown, although it has been shown that this trait is genetically determined, as is acquisition of bone mass (Rosen et al., 1994). Therefore, it is reasonable to hypothesize that premature graying might be a marker for a variety of genetic and non-genetic conditions such as myocardial infarction (Schnohr et al., 1995), congestive heart failure, cancer, stroke, pneumonia/bronchitis, cirrhosis of the liver, GI problems, or premature mortality. However, autopsy studies have not shown an association between these disorders and premature graying (Glasser, 1991). Therefore, the key to the significance of premature graying, if any, may come with further understanding of the pathophysiology of melanin loss within the hair follicle itself.

To our knowledge, no previous studies have examined the relation of balding to bone loss. However, balding has been examined as a marker for myocardial infarction (Schnohr, et al., 1995) because both conditions are related to androgen levels. Because BMD levels are associated with sex hormone levels (Schneider et al., 1997), a balding-BMD association is plausible.

The most common form of alopecia in men is believed to be due to excessive activity of androgens on the scalp where the hairs become miniaturized and pigment production is stopped (Hoffman, 2002). Other known and validated factors influencing the development of common baldness are few but include polygenic inheritance patterning, higher levels of 5-alpha reductase, which is responsible for converting testosterone into a more potent androgen, and aging (Hamilton, 1951;Hoffman, 2002;Price, 2003;Severi et al., 2003;). Many women with alopecia, however, have normal levels of circulating androgens. A recent trial of three treatments, cyproterone acetate (an anti-androgen), flutamide (an androgen receptor blocker), and finasteride (inhibits 5a-reductase activity), found only a modest improvement in alopecia with fluatmide, but not cyproterone acetate or finasteride (Carmina & Lobo, 2003). In 2006, Iorizzo et al. reported some improvement of hair loss in women taking finasteride simultaneously with oral contraceptives. Therefore differential associations with bone density and balding by gender might be observed, as is the case in the present study. Although free testosterone levels have not been associated with balding, androgen levels in the hair follicles themselves might be more predictive of bone density, especially when considered in conjunction with genetic factors for balding.

This study is advantageous, as the Rancho Bernardo cohort allows for control of many confounders associated with BMD, and this population has well-validated self-report accuracy(Criqui et al., 1978;Schneider et al., 1997). Information on current estrogen use, body mass index, exercise habits, smoking, alcohol consumption, use of thyroid medications, diuretics, glucocorticosteroids, and calcium supplements was available for use as covariates in the multivariate model. DEXA measurement, the gold standard for determination of bone mineral density (Schneider et al., 1997), was used to assess bone mass. In addition, the large sample size of this study makes it an important addition to the literature and indicates the likelihood of the stability of the estimates based on the data.

This study also has several limitations. Although participants in the Rancho Bernardo study were similar to Rancho Bernardo residents who chose not to participate (Criqui et al., 1978; Barrett-Connor & Kritz-Silverstein, 1999), the cohort consists of individuals who are middle-class, relatively well-educated, and have good access to medical care. This homogeneity, while being advantageous with regard to less confounding due to low socioeconomic status, education, and/or the effect of limited health care on survival, also means the study results may not generalize to other cohorts (Garland et al., 1992). The effects of endogenous estrogen on BMD may not have been adequately controlled, because estrogen levels were not measured continuously from early adulthood when they are presumed to have their maximum effect on a variety of body systems (Rogers et al., 2000). Finally, an important limitation for older individuals and particularly women who color their hair is poor recall of the age when graying of their hair was “almost complete.” In addition, accuracy or reliability for events over a span of 30 years may be questionable. Events like the extent of graying are gradual rather than discrete occurrences that may have affected recall and thus there may have been some misclassification, though less likely in men, who generally do not color their hair.

In summary, the results of the present study observed no association of premature graying with BMD, and sporadic associations of balding status with BMD in men and women. Significantly higher femoral neck (23%) and total hip (24%) BMD in balding women may be associated with estrogen used by more than two-thirds of this group of women compared with only half of the non-balding women. Future investigations should be aimed at understanding the mechanism of melanin depletion and ascertaining actual androgen levels within the hair follicle as a predictor of low BMD, as well as addressing differences in the pathophysiology of balding between men and women.