Results from this study suggest that PBM has been attained in the spine and femoral neck, but not in the radius or tibia, in 18- to 20-year-old men, in which an endosteal contraction and increase in cortical volumetric BMD is observed.
Introduction: Peak bone mass (PBM) is an important determinant for the risk of osteoporosis. In men, the age of attainment of PBM has been under some controversy. The objective of this study was to determine if peak bone mass had been attained, and whether it is site specific, in 18- to 20-year-old Swedish men.
Materials and Methods: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study consists of 1068 men, 18.9 ± 0.6 years of age. BMD was measured using both DXA and pQCT. Environmental factors, such as dietary intake and physical activity, were assessed through questionnaires. The independent predictors of BMD were assessed through multiple linear regression, including age, height, weight, calcium intake, smoking, and physical activity.
Results and Conclusions: We show, in a large well-characterized cohort, that age was not an independent predictor of BMD of the lumbar spine, femoral neck, or total body, indicating that peak BMD has been achieved in these skeletal sites, whereas it was an independent predictor of BMD of the radius, suggesting that peak BMD has not yet been attained in the long bones. pQCT analyses of the radius and the tibia revealed that age was associated with cortical volumetric BMD and endosteal contraction of the radius and tibia. These results show that the age of attainment of PBM is site specific.
THE RISK OF developing osteoporosis is dependent both on the magnitude of bone accumulated during growth and the rate of bone loss in adulthood.(1,2) Osteoporosis has now become a large public health burden not only in women but also in men.(3) The maximal attained bone mass in life, peak bone mass (PBM), is dependent primarily on genetic factors, but also on environmental factors such as physical activity and calcium intake.(4) PBM has been estimated to account for about one-half of the BMD variation up to 65 years of age.(1,2) BMD is a strong predictor of fracture, and each SD decrease in BMD has been associated with about a 2-fold increase in the age-adjusted hip fracture risk in postmenopausal women(5) and with a 3-fold risk increase in elderly men.(6)
In men, the age of attainment of PBM and its site specificity has been under some controversy. The age span of the attainment of PBM has ranged from late adolescence to the late 20s in various previous reports.(7–10) Previous studies investigating PBM have used DXA measurements, have not been able to discriminate between the cortical and the trabecular bone compartments, and have been quite restricted in regard to population size.(7,8)
Information about the age of PBM at different skeletal sites is of importance to make recommendations in prevention programs aimed at maximizing PBM. Furthermore, the mechanism by which bone mass increases once linear growth has ceased is not fully understood.
The objective of this study was to determine if PBM had been attained, and whether it is site specific, in 18- to 20-year-old Swedish men.
MATERIALS AND METHODS
The Gothenburg Osteoporosis and Obesity Determinants (GOOD) Study was initiated with the aim to determine both environmental and genetic factors involved in the regulation of bone and fat mass. Study subjects were randomly identified using national population registers, contacted by telephone, and asked to participate in this study. A total of 1068 men, 18.9 ± 0.6 (SD) years of age, from the greater Gothenburg area, were included. To be included in the GOOD study, subjects had to be >18 and <20 years of age and willing to participate in the study. There were no other exclusion criteria; 48.6% of the contacted study subject candidates agreed to participate and were included in this study. The majority of the subjects included were white (n = 1046), rendering only a small group of other ethnicity (including Hispanics and Asians; n = 22). A standardized questionnaire was used to collect information about amount of present physical activity (hours per week, duration in years), nutritional intake (dairy products, vegetables, and vitamin intake), smoking, and history of fracture, as well as fracture history in the subjects' families. Calcium intake was estimated from dairy product intake and semiquantitated into quintiles before values were used in linear regression analysis.
The GOOD study was approved by the ethics committee at Gothenburg University. Written and oral informed consent was obtained from all study participants. To determine whether the GOOD cohort was representative of the general young male population in Gothenburg, we compared the height and weight of the GOOD subjects with a group of 624 aged-matched, randomly selected conscripts, living in the same area as the GOOD subjects. Subjects in this population had an average height of 180.9 ± 6.9 cm, weighed 74.2 ± 11.3 kg, and had a body mass index (BMI) of 22.6 ± 3.0 kg/m2. There was no difference in height, weight, or BMI (using an independent-sample t-test) between these two cohorts, indicating that the GOOD cohort is representative of the general young male population of Gothenburg.
Height and weight were measured using standardized equipment. The CV values were <1% for these measurements.
Bone area (cm2), BMC (g), and areal BMD (aBMD; g/cm2) of the whole body, femoral neck (of the left leg), lumbar spine, and the nondominant arm (left or right radius) were assessed using the Lunar Prodigy DXA (GE Lunar Corp., Madison, WI, USA). The CVs for the aBMD measurements ranged from 0.5% to 3%, depending on application. The volumetric BMD (vBMD) of the femoral neck and of the lumbar spine was estimated using DXA scans as previously described.(11,12)
A pQCT device (XCT-2000, Stratec Medizintechnik, Pforzheim, Germany) was used to scan the distal leg (tibia) and the distal arm (radius) of the nondominant leg and arm, respectively. The pQCT was calibrated every week using a standard phantom and once every 30 days using a cone phantom provided by the manufacturer. A 2-mm-thick single tomographic slice was scanned with a voxel size of 0.50 mm. The cortical vBMD (mg/cm3), cortical BMC (mg/mm), cortical cross-sectional area (CSA, mm2), endosteal and periosteal circumferences (EC and PC), and cortical thickness (mm) were measured using a scan through the diaphysis (at 25% of the bone length in the proximal direction of the distal end of the bone) of the radius and tibia. Trabecular vBMD (mg/cm3) was measured using a scan through the metaphysis (at 4% of the bone length in the proximal direction of the distal end of the bone) of these bones. Tibia length was measured from the medial malleolus to the medial condyle of the tibia, and length of the forearm was defined as the distance from the olecranon to the ulna styloid process. The CVs were <1% for all pQCT measurements.
Bivariate correlations were tested using Pearson's coefficient of correlation. The independent predictors of the various bone parameters were tested using multiple linear regression analyses. Height, weight, physical activity, calcium intake, and smoking were included as covariates together with age in the regression analyses. The difference in aBMD of the radius between the oldest 10th percentile compared with the youngest 10th percentile was studied using an independent samples t-test. A p value <0.05 was considered significant.
Descriptive characteristics of age, anthropometrics, and bone variables as measured using DXA and pQCT are given in Table 1.
Table Table 1.. Anthropometrics and Bone Variables
Age was not correlated to aBMD, measured with DXA, of the total body, femoral neck, or lumbar spine (Figs. 1A-1C), indicating that PBM has been achieved at this age. Neither the estimated vBMD (calculated from DXA results) of the femoral neck (r = −0.01, p = 0.79) nor that of the lumbar spine (L3; r = −0.02, p = 0.57) was correlated to age. In contrast, aBMD of the radius was found to be correlated to age (Fig. 1D). Factors known to affect PBM, including calcium intake, physical activity, weight, height, and smoking, were used in a multiple linear regression model, together with age, to determine the independent predictors of the different bone parameters measured. In these analyses, age was an independent predictor of aBMD of the radius (β = 0.16 and p < 0.0001), but not of the other sites measured. aBMD of the radius was 5% higher in the oldest (n = 108) 10th percentile compared with the youngest 10th percentile (n = 104; p < 0.0001) of the cohort. Bone area of the radius was not correlated to age, suggesting that the outer dimensions of this bone were not altered by age.
pQCT measurements of the radius and tibia were used to determine vBMD and bone size of the trabecular and cortical bone compartments. These analyses showed that age was correlated to vBMD, thickness, and EC, but not to PC (Figs. 2A-2D) of the cortical bone in the diaphyseal region of the radius. Age was an independent predictor of cortical vBMD (radius: β = 0.29, p < 0.001; tibia: β = 0.15, p < 0.001), thickness (radius: β = 0.15, p < 0.001; tibia: β = 0.09, p < 0.01), and EC (radius β = −0.10, p < 0.001; tibia: β = −0.07, p < 0.01) in both the radius and tibia. Hence, increasing age was associated with an increased cortical thickness, mainly caused by a diminished EC. Trabecular vBMD of the radius (β = 0.08, p < 0.01) and of the tibia (β = 0.06, p = 0.02) was weakly correlated to age.
No correlation between age and height (r = 0.016 and p = 0.69) was found.
PBM is an important determinant for the risk of contracting osteoporosis.(13) The age of attainment of PBM has been under some controversy. Previous studies have been quite restricted in regard to population size and limited by the use of a 2-D measurement (aBMD) of the bone using DXA.(7,8) aBMD provided by DXA is dependent on bone size. Hence, a large bone will be falsely perceived as having higher aBMD.(14,15)
Some cross-sectional studies have indicated that PBM is not attained until late in the third decade in life,(9,10) whereas other reports have shown that only little bone mass accumulation seems to take place after the second decade in life.(16,17) In both females and males, data from longitudinal studies have shown that the rate of increase in bone mass of the femoral neck and lumbar spine slows markedly down in late adolescence.(7,18) In our large cohort of young men, we showed that age was not correlated to aBMD of the total body, femoral neck, or lumbar spine between ages 18-20, suggesting the attainment of peak bone mass at these skeletal sites. A few studies in females and males have shown a limited increase in radius aBMD (measured using DXA) after the second decade in life.(8,10,17) Because of the limitations of the DXA methodology, it has not yet been clarified whether this increment is caused by augmented vBMD of the cortical or trabecular bone or increased bone size. We detected a correlation between aBMD of the radius and age, indicating that PBM has not yet been achieved at this site in our cohort. Statistically adjusting for possible confounding factors, such as body size parameters and environmental factors (smoking, calcium intake, and physical activity) did not influence the correlation between age and radius aBMD. To evaluate the possible mechanism underlying this correlation, we used pQCT measurements of the long bones (i.e., the radius and tibia). Age was found to be a strong independent predictor of cortical vBMD, cortical thickness, and EC of both the radius and tibia. Hence, we hereby show that the cortical consolidation, which has previously been assumed (based on DXA measurements)(8) to take place after the cessation of linear growth, is mainly caused by increased mineralization of the cortical bone and augmented cortical thickness. In contrast to the subperiosteal expansion seen throughout adulthood,(19) we show that, during late adolescence, age is associated with an endosteal contraction but not with a periosteal expansion of the long bones. It should be noted that these results were obtained in a primarily white population and can not therefore necessarily be transferred to other ethnic groups.
In conclusion, this study is the largest cohort, with the most well-characterized subjects thus far, investigating the age for PBM at different skeletal sites in men. Our results show that PBM has been attained in the total body, femoral neck, and lumbar spine, but not yet in the cortices of the long bones in 18- to 20-year-old men. Furthermore, our study gives novel information about the mechanism behind the age-dependent increase in PBM of the cortices in the long bones after the linear growth has ceased, showing that it is mainly caused by an increase in mineralization (vBMD) but also to an endosteal contraction (EC), whereas the outer dimension (PC) of the cortical bone is not affected (Fig. 2E). Hence, active measures, such as increased calcium intake, in young adulthood might have the ability to stimulate PBM in the cortices of the long bones in older ages than previously suggested.
This study was supported by the Swedish Medical Research Council, the Swedish Foundation for Strategic Research, the European Commission, the Lundberg Foundation, the Torsten and Ragnar Söderberg's Foundation, the Emil and Vera Cornell Foundation, the Novo Nordisk Foundation, the Petrus and Augusta Hedlunds Foundation, the Västra Götaland Foundation, and the Göteborg Medical Society.