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Bone Loss in Young HIV+ Men 'Lifestyle Risk'
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CROI: LOW BONE MASS IN BEHAVIORALLY HIV-INFECTED YOUNG MEN ON ANTIRETROVIRAL THERAPY: Adolescent Trials Network (ATN) Protocol 021B (03/13/11) - 'it is lifestyle that predisposed these young men to bone loss'
"Researchers recommend monitoring, exercise, vitamin D to prevent future fracture risk....quit smoking and limit alcohol consumption"
"from Jules: these data may suggest young men who get HIV-infected and go on HAART are at greater risk for greater bone loss because they may be predisposed to developing bone loss. Although the study did not find an association between illegal drug use & bone loss other studies have suggested heroin use associated with bone loss; studies have found excessive alcohol use associated with bone loss; smoking cigarettes is associated with bone loss & lifestyle associated with using drugs like not eating properly etc. Also being skinny (low BMI), and not having yet reached peak bone mass due to their young age likely contribute to risk for bone loss" ......so this study may be misleading because the lifestyle of these youg men appeared to predispose them to bone loss; hit the link above to see the original presentation at CROI 2011 for this study where you can see 70% drank alcohol, 60% had a history of illegal substance abuse, only 50% regularly exercised, and low intake of calcium and vitamin D, and individuals tended to be skinny - all risk factors for bone loss. SO the real message is these HIV+ young men had many lifestyle risk factors for bone loss & this puts them at risk for fractures later on in life and perhaps greater risk for premature fractures. We know that in the general population fractures in the elderly leads to premature death.
from the study:
"Some studies suggest that the risk of low BMD in HIV-infected adult men may be similar to or greater than the risk in HIV-infected women [13, 14]. Perinatally HIV-infected males in the final stage of pubertal development have shown more evidence of low bone mass than HIV-infected females [15]."
"The study was not designed to determine the cause of the bone loss and cannot rule out the possibility that low bone mass preceded the young men's HIV infection. The researchers noted that all the young men had several risk factors for bone loss, such as tobacco and alcohol use, and low intake of calcium and vitamin D (needed to absorb calcium.)....The researchers found that the HIV-positive participants who had not yet begun treatment tended to have less body fat than either their counterparts on medication or the study's HIV-negative participants."
"We report evidence of low bone mass in behaviorally HIV infected young men on ART, particularly those on ART regimens that include a PI. Our results are consistent with those of other cross-sectional studies reporting lower bone density in groups of HIV-positive adults [1] and lower bone density or content and/or quality in perinatally HIV infected children [15, 19-22], when compared with HIV-negative controls. However, the adults and youth in these other studies had longer reported durations of HIV infection and, as a result, longer exposure to ART. To our knowledge, this is the first report of low bone mass among youth who acquired HIV infection relatively recently, presumably after the onset of sexual debut during late stages of puberty, and have relatively less exposure to ART."
"Peak bone mass is approached or achieved during adolescence and early adulthood and is the major determinant of bone mass during adulthood [16]. It is likely that many of our participants had not yet achieved peak bone mass.....it is reasonable to expect that bone loss or impaired accrual of bone mass among HIV-infected youth on ART may place them at greater risk for fractures in adulthood."
"A unique feature of this study is the inclusion of a sizeable HIV-infected but ART-naïve group, which allowed us to examine the potential separate contributions of untreated HIV infection and use of ART on bone mass. In the ART-naïve group, total and regional fat were lower than both seronegative controls and HIV-infected participants on ART, consistent with the known effects of untreated HIV infection [25]. However, we saw little evidence of loss or impaired accrual of bone mass in this group. Thus, in these youth who had acquired HIV infection relatively recently, the effect of HIV infection per se on bone mass appeared to be minimal"
"HIV-positive men (N=199) and HIV-negative controls (N=53), ages 14-25 years, were studied at 15 ATN sites. HIV-positive participants were recruited on the basis of ART status: ART-naïve (N=105) or on a regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI; N=52) or protease inhibitor (PI; N=42). Bone mineral density (BMD) and content (BMC) and body composition were measured by dual-energy X-ray absorptiometry (DXA).
in this cross-sectional study......majority of participants being African American and 28% of Hispanic ethnicity. The median age was 21 years in both HIV-positive and HIV-negative groups"
"More than two-thirds of participants in each group reported alcohol use. Cigarette smoking was reported by more than 30% of participants in each group, and slightly more than half reported some kind of regular exercise. There was significantly more cocaine use among HIV-positive than HIV-negative participants (P=0.01). There were trends toward greater use of amphetamines and cannabinoids among HIV-positive participants, but these were not statistically significant. Self-reported vitamin D intake was significantly higher in the HIV-positive group, but median levels of vitamin D intake in both groups were below the current level recommended by the Institute of Medicine [18]. Median calcium intake did not differ between groups."
"All HIV-infected participants had acquired HIV infection through risk behavior (i.e., not acquired perinatally or from transfusion of blood products)"
"Among the HIV-positive groups, the median reported time since HIV diagnosis ranged from 1.3 years in ART-naive to 2.2 years in the PI group"
"Weight, BMI, and total LBM were significantly lower in the ART-naïve and NNRTI groups, compared with the HIV-negative controls. Total body fat and trunk fat were lower in the ART-naïve group, both when compared with the HIV-negative group and when compared with each HIV-infected group on ART. Arm and leg fat were lower in both the ART-naïve and NNRTI groups, compared with HIV-negative controls. Among the three HIV-infected groups, the ART-naïve group had significantly less arm fat than either of the two groups on ART, and leg fat in the ART-naïve group was significantly lower than in the PI group."
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NIH Press Release
Tuesday, June 19, 2012
NIH study finds HIV-positive young men at risk of low bone mass - Full Text of Study in CID below
Researchers recommend monitoring, exercise, vitamin D to prevent future fracture risk....quit smoking and limit alcohol consumption."
Some studies suggest that the risk of low BMD in HIV-infected adult men may be similar to or greater than the risk in HIV-infected women [13, 14]. Perinatally HIV-infected males in the final stage of pubertal development have shown more evidence of low bone mass than HIV-infected females [15].
Young men being treated for HIV are more likely to experience low bone mass than are other men their age, according to results from a research network supported by the National Institutes of Health. The findings indicate that physicians who care for these patients should monitor them regularly for signs of bone thinning, which could foretell a risk for fractures. The young men in the study did not have HIV at birth and had been diagnosed with HIV an average of two years earlier.
Earlier studies have shown that adults with HIV also have bone loss and increased risk for bone fractures, associated in part with the use of certain anti-HIV medications.
"The young men in the study had been taking anti-HIV medications for a comparatively short time, yet they still had lower bone mineral density than other men their age," said co-author Bill G. Kapogiannis, M.D., of the Pediatric, Adolescent, and Maternal AIDS Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). "These findings suggest a short-term impact of HIV therapy on bone at ages when people are still growing and building bone mass. This raises concern about the risk of fracture as they age."
For the HIV-infected young men, on average, bone density in the hip was 5-8 percent lower, and in the spine 2-4 percent lower, than for study participants without HIV.
The study was not designed to determine the cause of the bone loss and cannot rule out the possibility that low bone mass preceded the young men's HIV infection. The researchers noted that all the young men had several risk factors for bone loss, such as tobacco and alcohol use, and low intake of calcium and vitamin D (needed to absorb calcium.)
The study was conducted by lead authors Kathleen Mulligan, Ph.D., of the University of California, San Francisco; Grace Aldrovandi, M.D., of Children's Hospital Los Angeles and the University of Southern California; Dr. Kapogiannis, and seven other researchers affiliated with the NICHD-supported Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN).
Their findings appear in Clinical Infectious Diseases.
Additional funding was provided by the NIH's National Institute on Drug Abuse, the National Institute of Mental Health, and the National Center for Research Resources and the National Center for Advancing Translational Sciences.
Some 250 teens and young men (14 to 25 years old) participated in the study. About 88 percent of the study participants identified themselves as African-American or Hispanic and all lived in urban areas. The participants underwent whole body scans to measure their bone density as well as the distribution of fat and lean muscle mass in certain regions of their bodies. Participants also answered questions about their medical history, and diet, exercise and other lifestyle habits.
The researchers calculated the density of bones in the body as a whole, as well as the spine and hipbones. These bones are more susceptible than other bones to bone loss, Dr. Mulligan explained. The researchers also assessed total body fat and amounts of fat in the arms, legs and trunk.
The researchers found that the HIV-positive participants who had not yet begun treatment tended to have less body fat than either their counterparts on medication or the study's HIV-negative participants.
Both bone density and the calcium and other mineral content of bones tended to be lowest in participants taking medication for HIV. Youth with HIV who had not begun treatment had higher bone mass levels than HIV positive youth who were on anti-HIV regimens, but lower bone mass levels than youth who did not have HIV. Participants' responses to questions about diet indicated that at least half of them did not consume sufficient calcium or vitamin D. The researchers also found that more than 30 percent of all the participants smoked. Half said they did not get regular exercise. Smoking and lack of exercise can contribute to weaker bones. The study authors noted that additional studies are needed to follow HIV-positive young men long term to determine whether bone loss during adolescence increases the risk of fractures later in life.
"None of the young men we saw is in immediate risk of fracture," said Dr. Mulligan. "However, our results indicated that it would be a good idea for young men newly diagnosed with HIV to make sure they exercise, get enough calcium and vitamin D, quit smoking and limit alcohol consumption."
Researchers in the ATN Network previously found that vitamin D supplements might help protect the bones of people taking the anti-HIV drug tenofovir.
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Low Bone Mass in Behaviorally HIV-Infected Young Men on Antiretroviral Therapy: Adolescent Trials Network (ATN) Study 021B
Clin Infect Dis. (June 2012)
Kathleen Mulligana, D. Robert Harrisb, Patricia Emmanuelc, Roger A. Fieldingd, Carol
Worrelle, Bill G. Kapogiannise, Dina Monteb, John Sleasmanf, Craig M. Wilsong, and Grace
M. Aldrovandih for the ATN 021 Protocol team
aUniversity of California and San Francisco General Hospital, San Francisco, CA; bWestat,
Rockville, MD; cUniversity of South Florida, Tampa, FL; dFriedman School of Nutrition Science
and Policy, Tufts University, Boston, MA; ePediatric, Adolescent and Maternal AIDS Branch,
National Institute of Child Health and Human Development, NIH, Bethesda, MD; fUniversity of
South Florida, St. Petersburg, FL; gUniversity of Alabama at Birmingham, Birmingham, AL;
hChildren's Hospital Los Angeles, University of Southern California, Los Angeles, CA
Abstract
Background Peak bone mass is achieved in adolescence/early adulthood and is the key determinant of bone mass in adulthood. We evaluated the association of bone mass with HIV infection and antiretroviral therapy (ART) during this critical period among behaviorally HIV-infected young men and seronegative controls.
Methods HIV-positive men (N=199) and HIV-negative controls (N=53), ages 14-25 years, were studied at 15 ATN sites. HIV-positive participants were recruited on the basis of ART status: ART-naïve (N=105) or on a regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI; N=52) or protease inhibitor (PI; N=42). Bone mineral density (BMD) and content (BMC) and body composition were measured by dual-energy X-ray absorptiometry (DXA). Results were compared across groups by linear modeling. Bone results were adjusted for race, BMI, and type of DXA (Hologic/Lunar).
Results The HIV-positive and HIV-negative groups had comparable median age (21 years) and racial/ethnic distribution. Median times since HIV diagnosis were 1.3, 1.9, and 2.2 years in the ART-naïve, NNRTI, and PI groups, respectively (P=0.01). Total and regional fat were significantly lower in the ART-naïve group, compared with seronegative controls. Mean BMD and Z-scores were generally lower among HIV-positive participants on ART, particularly in the PI group. Average Z-scores for the spine were below zero in all four groups, including controls.
Conclusion Young men on ART with a relatively recent diagnosis of HIV infection have lower bone mass than controls. Longitudinal studies are required to determine the impact of impaired accrual or actual loss of bone during adolescence on subsequent fracture risk.
BACKGROUND
Low bone mineral density (BMD) is frequently observed in persons with HIV infection [1, 2]. Studies have reported increasing fracture rates among older HIV-infected adults [3-5]. Risk factors for low BMD or fractures include initiation and use of antiretroviral therapy (ART) [6-9], specific antiretrovirals [7, 8, 10], inflammation [11], and hepatitis B or C virus co-infection [12], as well as conventional lifestyle factors such as cigarette smoking, alcohol or drug use, age, low body weight, white race, and inactivity [2]. Some studies suggest that the risk of low BMD in HIV-infected adult men may be similar to or greater than the risk in HIV-infected women [13, 14]. Perinatally HIV-infected males in the final stage of pubertal development have shown more evidence of low bone mass than HIV-infected females [15].
Peak bone mass is achieved or approached during adolescence [16]. Failure to accrue bone during this critical period of growth could confer greater risk for fracture later in life. This risk is likely to be exacerbated in HIV-infected youth, who face extended exposure to HIV, ART, and other HIV-related comorbidities during adulthood. In the current study, we examined the effects of HIV infection and ART on bone density in behaviorally HIV-infected young men and seronegative controls.
METHODS
HIV-positive young men (N=199), ages 14-25 years, were enrolled in this cross-sectional study between April, 2006 and July, 2007 at 15 clinical sites on behalf of the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) in the United States and Puerto Rico. Recruitment was based on current use of ART as follows: antiretroviral naïve (ART-naive; N=105); on an ART regimen that contained a non-nucleoside reverse transcriptase inhibitor (NNRTI) for >3 months (NNRTI; N=52); or on an ART regimen that included a PI for >3 months (PI; N=42). Participants in the NNRTI group had not received >6 months of PI in total and must have received none in the preceding year. Likewise, participants in the PI group had not received >6 months of NNRTI and must have received none in the preceding year. A seronegative control group (N=53) from the same age range was recruited at the same clinical sites. Recruitment of this latter group was initiated after the first 50 HIV-infected participants were enrolled and monitored throughout the recruitment period to assure that the distributions of sociodemographic characteristics were similar to those of HIV-positive participants. All HIV-infected participants had acquired HIV infection through risk behavior (i.e., not acquired perinatally or from transfusion of blood products), were Tanner stage 4 or 5, and had accessible medical and medication histories. Exclusion criteria for all participants included type 1 diabetes mellitus and use of androgens or systemic glucocorticoids. Transgender youth were excluded. The institutional review board at each clinical site approved the study, and appropriate written informed consent/assent was obtained before enrollment.
Assessments
Height and weight were measured following standard protocols. Separate dual-energy X-ray absorptiometry (DXA) scans of the left hip, spine, and whole-body were performed with central analysis at Tufts University by readers who were blinded to HIV status and ART regimen. A standard phantom was scanned on each DXA instrument used in the study. Machine-generated Z-scores for spine (L1-L4) and hip BMD were used. Z-scores for total body bone mineral content (BMC) were calculated using norms developed at Baylor University [17]. These latter norms have been validated only up to age 22 years and, thus, could be applied to only 66% of participants. Total and regional fat and lean body mass (LBM) were obtained from the whole-body scans.
All participants underwent detailed medical histories, including documentation of substance use, and, in HIV-positive participants, age at HIV diagnosis, ART and HIV disease histories, current and peak HIV-1 RNA, and current and nadir CD4+ T cell measures. All participants completed food frequency (Block Dietary Systems, NutritionQuest, Berkeley, CA) and lifestyle questionnaires that included questions about smoking, alcohol use, and regular exercise (defined as exercising more than once weekly).
RESULTS
Demographic and Lifestyle Characteristics
The median age was 21 years in both HIV-positive and HIV-negative groups (P=0.13; Table 1). By design, the racial and ethnic distribution within the two groups was balanced, with the majority of participants being African American and 28% of Hispanic ethnicity. More than two-thirds of participants in each group reported alcohol use. Cigarette smoking was reported by more than 30% of participants in each group, and slightly more than half reported some kind of regular exercise. There was significantly more cocaine use among HIV-positive than HIV-negative participants (P=0.01). There were trends toward greater use of amphetamines and cannabinoids among HIV-positive participants, but these were not statistically significant. Self-reported vitamin D intake was significantly higher in the HIV-positive group, but median levels of vitamin D intake in both groups were below the current level recommended by the Institute of Medicine [18]. Median calcium intake did not differ between groups.
HIV Disease-Related Data
Among the HIV-positive groups, the median reported time since HIV diagnosis ranged from 1.3 years in ART-naive to 2.2 years in the PI group (P=0.01; Table 2). Current CD4 measures did not differ significantly among groups. However, among those on ART, nadir CD4 (both absolute count and percent) and current HIV RNA were lower, and peak HIV RNA levels higher, compared with the ART-naïve group. Virologic suppression, defined as an HIV RNA level ≤400 copies/mL, was seen in 92% and 74% of participants in the NNRTI and PI groups, respectively, but in only 5% of ART-naïve participants (P<0.001). CDC staging differed significantly among HIV-positive groups (P<0.001), with a greater proportion of ART-naïve participants classified in stage A/none and a smaller proportion in stage C, than among the groups receiving ART. Two participants, both in the PI group, were hepatitis C virus (HCV) antibody positive. Among participants in the NNRTI group, 96% were using efavirenz, 4% nevirapine, 71% emtricitabine, 63% tenofovir, 27% lamivudine, 25% zidovudine, 12% didanosine, and 2% abacavir.
Among participants in the PI group, 90% were on a ritonavir-containing regimen (either as lopinavir/ritonavir or other use of ritonavir in boosting or therapeutic doses); 57% were using atazanavir, 33% lopinavir, 7% fosamprenavir, 2% nelfinavir, 79% tenofovir, 69% emtricitabine, 21% lamivudine, 19% zidovudine, 12% abacavir, 7% didanosine, and 2% stavudine. Use of tenofovir did not differ significantly between the NNRTI and PI groups (P=0.12).
Body Composition
Average height did not differ significantly among groups (Table 3). Weight, BMI, and total LBM were significantly lower in the ART-naïve and NNRTI groups, compared with the HIV-negative controls. Total body fat and trunk fat were lower in the ART-naïve group, both when compared with the HIV-negative group and when compared with each HIV-infected group on ART. Arm and leg fat were lower in both the ART-naïve and NNRTI groups, compared with HIV-negative controls. Among the three HIV-infected groups, the ART-naïve group had significantly less arm fat than either of the two groups on ART, and leg fat in the ART-naïve group was significantly lower than in the PI group.
Bone Mass
Both total body BMD and Z-scores for total BMC differed significantly among groups, whereas total body BMC did not (Table 4). In pairwise comparisons, the PI group had lower total body BMD than both seronegative and HIV-infected ART-naïve controls, and both groups on ART had lower total body BMC Z-scores than seronegative controls. In the total hip, BMD was significantly lower in both groups on ART relative to the seronegative controls, and BMD in the PI group was also lower relative to the HIV-positive, ART-naïve group. Total hip BMD Z-scores in the PI group were significantly lower than those in both the seronegative and the HIV-positive ART-naïve groups. In the femoral neck, BMD and BMD Z-scores were significantly lower only in the PI group, relative to both the HIV-negative and HIV-positive ART-naïve groups.
Results for other hip regions (trochanter, Ward's) followed similar patterns, with BMD and BMD Z-scores in each of these subregions being significantly lower in the PI group, compared with the HIV-negative and ART-naïve controls (data not shown). Spine (L1-L4) BMD tended to be lower in the groups on ART, but differences did not achieve a level of statistical significance when results in all four groups were considered (P=0.083). Among the three HIV-infected groups, spine BMD was significantly lower in the PI group compared with the ART-naïve group. The spine Z-scores were below zero in all four groups and were significantly lower only in the PI group, compared with both HIV-negative and HIV-positive ART-naïve controls. In post-hoc analyses, we found no statistically significant association of low bone mass with current tenofovir use, regular exercise, or use of alcohol, amphetamines, cocaine, or marijuana (data not shown). Likewise, excluding the two HCV-infected participants in the PI group from the analysis did not materially affect the results.
CONCLUSIONS
We report evidence of low bone mass in behaviorally HIV infected young men on ART, particularly those on ART regimens that include a PI. Our results are consistent with those of other cross-sectional studies reporting lower bone density in groups of HIV-positive adults [1] and lower bone density or content and/or quality in perinatally HIV infected children [15, 19-22], when compared with HIV-negative controls. However, the adults and youth in these other studies had longer reported durations of HIV infection and, as a result, longer exposure to ART. To our knowledge, this is the first report of low bone mass among youth who acquired HIV infection relatively recently, presumably after the onset of sexual debut during late stages of puberty, and have relatively less exposure to ART.
Peak bone mass is approached or achieved during adolescence and early adulthood and is the major determinant of bone mass during adulthood [16]. It is likely that many of our participants had not yet achieved peak bone mass. It is critically important to maintain bone health during this period to optimize an individual's chances of achieving his or her genetically determined potential for peak bone mass. Factors that interfere with achieving this potential during adolescence may further increase subsequent fracture risk, even if bone loss during adulthood is minimized. Although low bone mass observed in people with HIV infection has not yet been directly related to fractures, there is increasing evidence that older persons with HIV infection have higher fracture rates than are seen in HIV-negative populations [3-5, 23]. Currently available fracture risk assessment tools such as FRAX cannot be applied to young persons [24]. However, it is reasonable to expect that bone loss or impaired accrual of bone mass among HIV-infected youth on ART may place them at greater risk for fractures in adulthood.
A unique feature of this study is the inclusion of a sizeable HIV-infected but ART-naïve group, which allowed us to examine the potential separate contributions of untreated HIV infection and use of ART on bone mass. In the ART-naïve group, total and regional fat were lower than both seronegative controls and HIV-infected participants on ART, consistent with the known effects of untreated HIV infection [25]. However, we saw little evidence of loss or impaired accrual of bone mass in this group. Thus, in these youth who had acquired HIV infection relatively recently, the effect of HIV infection per se on bone mass appeared to be minimal. We should point out that although we adjusted our DXA results for race, our population was predominantly non-white, and our results may not apply to young men from other racial/ethnic groups.
The role of ART in bone loss is not fully understood. Studies in ART-naïve HIV-infected adults have consistently shown a statistically significant decrease in BMD over the first 6-12 months after ART initiation that typically averages between 4 and 6% [6-8, 26] and appears to stabilize or partially reverse after that time [7, 26, 27]. Although decreases in BMD have been reported with initiation of any ART regimen, the magnitude of the decrease is consistently greater in groups initiating regimens that contain tenofovir [7, 8, 26] and, in most cases, is greater with initiation of regimens containing a PI, when compared with those that contain an NNRTI but no PI [8, 10]. Longitudinal studies performed in HIV-infected persons on ART are less consistent, with some showing stability of BMD [28-30] and others showing continuing loss [9, 14, 31]. Likewise, the effect of cumulative exposure to tenofovir is unclear, with some studies showing continuing loss and others relative stability [9, 27, 29]. The mechanisms by which ART induces bone loss are as yet unknown.
Mean spine Z-scores were below zero in all four groups, including the seronegative control group. The latter was an unexpected finding, since one would expect the average Z-scores among this healthy group of young men to be zero. A similar result was reported in preliminary results of analysis of baseline DXA scans in an international HIV pre-exposure prophylaxis (PrEP) study in seronegative men with a median age of 25 years [32]. In addition, Liu et al. [33] reported a higher than expected prevalence of low bone mass among adult men in the U.S. (median age 48) who underwent screening or baseline testing for another PrEP study.
Finally, Grijsen et al. [34] reported a high prevalence of low bone density among 33 Dutch men (mean age 38) with primary HIV infection. The authors speculated that their findings may reflect an acute effect of immune activation on bone mass but acknowledged that low bone mass in their population may also have predated the acquisition of HIV. Although we cannot exclude the possibility that the normative data used to generate the standard deviations (T- or Z-scores) do not represent the current distribution of BMD among healthy younger men, these findings warrant further investigation. They are also of particular relevance given recent successes with pre-exposure prophylaxis as an HIV prevention intervention among at-risk populations of young men (e.g. [35]).
We acknowledge the well-described shortcomings of the use of DXA, which provides a two-dimensional measure of bone density that may be more prone to misinterpretation in younger populations that are still undergoing linear growth [36]. We also acknowledge the resulting challenges of characterizing bone mass in a population that spans the dynamic developmental period of adolescence and early adulthood (14-25 years). Accordingly, we would urge particular caution in interpreting the hip data and all Z-scores reported here, in accordance with the explicit caveat from the International Society for Clinical Densitometry that the diagnosis of osteoporosis cannot be made on the basis of BMD results alone in this age group [37]. In the U.S., a large longitudinal study of bone mass in children has been initiated and has already provided valuable normative data for use of DXA in individuals up to age 20 [38], and the anticipated availability of additional normative data in years to come will greatly enhance the ability of researchers and clinicians to characterize bone mass in individuals during this critical stage in bone development. Techniques such as quantitative CT would no doubt provide more accurate assessment of bone mass, but limited availability and substantial expense for research in large groups of participants, as well as radiation exposure, make this technology less suitable for multicenter use in an adolescent population.
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