Physical fitness effect on bone mass is mediated by the independent association between lean mass and bone mass through adolescence: a cross-sectional study

We studied 278 adolescents (169 females) aged 13.0–18.5 years to elucidate whether an independent effect of physical fitness and lean mass in the differences between male and female bones can be detected. Lean and fat masses and bone mineral content (BMC) were measured with DXA. Physical fitness was evaluated with six different tests included in the EUROFIT test battery (flexibility, isometric, dynamic and endurance strength, speed, and cardiovascular fitness). To test the independent relationship between physical fitness and bone mass, multiple regression analysis was applied, including lean mass, age, and Tanner development as covariates. The males had a 43% lower fat mass and 40% and 16% higher lean mass and total BMC compared with the females (all P < 0.05). After adjustment for differences in body size and lean mass, the females exhibited a 7.4% higher BMC than the males (P < 0.05). The multiple regression analysis showed that lean mass had an independent relationship with bone mass (P < 0.001), explaining 67% of the total variance in whole-body BMC. In males, change in R ² was 0.658 for hand grip and 0.035–0.151 for the rest of physical fitness-related variables; but 0.019–0.042 in females (all P–0.001); however, the independent relationships between physical fitness and bone disappeared after controlling for lean mass. In conclusion, it is likely the differences between male and female in bone mass could be explained by differences in lean mass and physical fitness.     

Growth and Bone Mineral Accretion During Puberty in Chinese Girls: A Five‐Year Longitudinal Study

There are few longitudinal data on bone development during puberty in children with low calcium intake. This 5‐yr longitudinal study showed that, in Chinese girls, the mean apparent calcium retention efficiency during puberty was 40.9%, PHV occurred at 3–0 yr before menarche, and peak bone mineral accretion occurred 1 yr later than PHV. Chinese girls have high calcium retention efficiency during puberty. Introduction: There are few longitudinal data on bone development during puberty in children with low dietary calcium intake. The aim of this study was to examine the rate of growth and bone mineral accretion and study the predictors of total body BMC during puberty in a 5‐yr longitudinal study with Chinese girls. Materials and Methods: Ninety‐two girls, 9.5–10.5 yr of age at baseline, from the unsupplemented control group of a school milk intervention trial were included in this analysis. Data on anthropometric measurements, total body BMC as assessed by DXA, and calcium intake as assessed by a 3‐day food record were obtained at baseline and 1, 2, 4, and 5 yr. Results: The mean age of menarche was 12.1 ± 1.0 yr. The mean annual rate of bone mineral accretion was 197.4 g/yr during the follow‐up period, representing a calcium accretion rate of 162.3 mg/d. This calcium retention rate and the average dietary calcium intake of 444.1 mg/d gave an apparent calcium retention efficiency of 40.9%. Peak height velocity (PHV) occurred at 3–0 yr before menarche. Peak bone mineral accretion occurred 1 yr later than PHV. There was a decrease in size‐corrected BMD in the year before menarche. In the linear mixed‐effects model analysis containing body size and lifestyle factors, we found that height, body weight, and calcium intake were significant independent predictors of total body BMC. Conclusions: Chinese girls with low habitual dietary calcium intake have high calcium retention efficiency during puberty. Because calcium intake is a significant predictor of total body BMC, increasing dietary calcium intake may have beneficial effects on bone mineral accretion in these girls.     

Long‐term survival after kidney transplantation in an HIV‐positive patient

Abstract: Only a decade ago, human immunodeficiency virus (HIV)‐seropositivity was considered an absolute contraindication for organ transplantation. With the currently available experience, it is no longer justified to deny HIV‐positive patients access to transplantation. To the best of our knowledge, we here present the longest surviving HIV‐positive patient after renal transplantation. The follow‐up period after renal transplantation in this HIV‐positive female is now 13 yr and she is in good general condition with excellent renal function. Throughout her post‐transplant follow‐up, we encountered a number of problems that are illustrative of the HIV‐positive patient.     

Gain in mass density of bone following strenuous physical activity

A group of 223 military recruits aged 18-21 years underwent strenuous physical training for a period of 14 weeks. The absolute bone density of the distal tibia in both lower limbs was measured before the training period and at its end. The density was determined by the Compton scattering technique, which has been developed in our laboratory; this method provides the bone mass of all bone constituents per unit volume. The distribution curve of the bone density in both tibiae shifted to higher values at the end of the training period. The mean bone density in the right and left tibia increased significantly by 7.5%. This study indicates that following an intensive physical exercise regime, a significant increase in the mass density of bone can be obtained in young adults within a short period.     

Long‐term critical issues in pediatric renal transplant recipients: a single‐center experience

Data on long‐term outcomes after pediatric renal transplantation (Tx) are still limited. We report on a 20‐year single‐center experience. Medical charts of all consecutive pediatric Tx performed between 1987 and 2007 were reviewed. Data of patients who had been transferred to adult units were extracted from the French databases of renal replacement therapies. Outcomes were assessed using Kaplan–Meier and Cox models. Two hundred forty Tx were performed in 219 children (24.1% pre‐emptive and 17.5% living related donor Tx). Median age at Tx was 11.1 years and median follow‐up was 10.4 years. Patient survival was 94%, 92%, and 91% at 5, 10, and 15 years post‐Tx, respectively. Overall, transplant survival was 92%, 82%, 72%, and 59% at 1, 5, 10, and 15 years post‐Tx, respectively. The expected death‐censored graft half‐life was 20 years. Sixteen patients developed malignancies during follow‐up. Median height at 18 years of age was 166 cm in boys and 152 cm in girls with 68% of patients being in the normal range. The proportion of socially disadvantaged young people was higher than in general population. Excellent long‐term outcomes can be achieved in pediatric renal Tx, but specific problems such as malignancies, growth, and social outcome remain challenging.     

Long‐term effects of intermittent androgen suppression on testosterone recovery and bone mineral density: results of a 33‐month observational study

OBJECTIVE

To investigate changes in bone mineral density (BMD) and osteoporosis, over 3 years of intermittent androgen‐suppression therapy (IAST).

PATIENTS AND METHODS

This was a Phase II individual cohort study of 72 patients with prostate cancer without metastatic bone disease, enrolled between 1999 and 2002. Patients had 9 months flutamide (250 mg, three times daily) and leuprolide (22.5 mg, 3‐monthly depot) after which, patients ceased therapy providing that their PSA levels were <4 ng/mL. AST re‐commenced when the PSA level exceeded the pretreatment level or was >20 ng/mL. BMD for hip and spine was the primary endpoint; assessed at baseline; completion of initial treatment period; and at 1 and 2 years after initial treatment (POST period).

RESULTS

Osteoporosis increased from 7% at baseline to 10% at 3 years. The BMD declined after 9 months treatment, at ?1.9% and ?3.3% at hip and spine, respectively (P < 0.001). Subsequent BMD decline in the POST period was attenuated; at 1 years and 2 years later, hip ?0.6% (not significant), and ?0.8% (P < 0.014), and spine +1.0% and +0.2% (not significant). The BMD change in those remaining ‘off’ therapy for 2 years (n = 20) was strongly associated with the level of testosterone recovery; a peak testosterone level of <5 nmol/L associated with a greater then normal physiological loss. Testosterone recovery was less likely in older men.

CONCLUSION

The attenuation of spine and hip BMD decline after 3‐year IAST compared with those reported for continuous AST appears to be due to testosterone driven BMD recovery in the POST period. Failure of testosterone recovery was associated with worse final BMD. By reducing the potential risk for adverse bone complications, intermittent therapy may become an important consideration when the therapeutic ratio is narrow.     

Long‐term results after excision of breast mass using a vacuum‐assisted biopsy device

Background: The excision of breast lesions using an ultrasound‐guided vacuum‐assisted biopsy device (VABD) is a widely used technique for the diagnosis and treatment of breast disease, but the results of long‐term follow‐up after VABD excision of benign breast tumours have not been reported. The purpose of this study was to evaluate the results of long‐term follow‐up after complete excision of benign breast tumours using an ultrasound‐guided VABD. Methods: This is a retrospective clinical study. Between January 2001 and December 2004, patients who had undergone VABD excision of benign breast tumours and been followed up by clinical examination and ultrasonography for 2 years or more were included. Results: One hundred eighty‐four cases representing 153 patients were studied. The median follow‐up period was 33 months (range, 24–67 months). All lesions were histologically benign. The mean size of the lesions was 1.09 ± 0.57 cm (range, 0.3–3.03 cm). Within 2 years after VABD excision, residual lesions were detected in 10% of patients sonographically, but after 2 years or more, residual masses were found in 6.5% of patients. Scar changes also decreased from 36.0% to 15.8% during the period of follow‐up. Finally, the benign breast tumours were completely excised without residual masses in 93.5% of the participant patients. Residual masses developed in two fibroadenoma cases (1.08%); one was re‐excised and the other was followed serially. Conclusion: Ultrasound‐guided VABD excision is a minimally invasive technique for the complete removal of benign breast tumours. The results of this long‐term follow‐up of VABD excisions are comparable to conventional methods.     

Adverse interaction of low‐calcium diet and low 25(OH)D levels on lumbar spine mineralization in late‐pubertal girls

No consensus has been reached on the serum 25‐hydroxyvitamin D [25(OH)D] levels required to ensure optimal bone health around menarche. We searched for a possible interaction of 25(OH)D levels and calcium intake on lumbar spine mineralization and on biologic features of bone metabolism in healthy late‐pubertal girls. Lumbar spine parameters (ie, area, mineral content, and density) and calcium intake were evaluated in 211 healthy white adolescent girls at pubertal stages IV–V (11 to 16.9 years), together with biologic markers of calcium and bone metabolism and with International External Quality Assessment Scheme for Vitamin D Metabolite (DEQAS)–validated serum 25(OH)D levels. A high prevalence of 25(OH)D levels ≤ 30 nmol/L (41%), ≤40 nmol/L (61%), and ≤50 nmol/L (70%) was found during winter–spring. Parathyroid hormone (PTH) levels were inversely associated with 25(OH)D levels (p = .0021). In contrast, lumbar spine mineral content and density were not associated with 25(OH)D, excepted when calcium intake was below 600 mg/day (p = .0081). Girls with such low calcium intake and 25(OH)D levels of 40 nmol/L or less (9% of the cohort) had a 0.4 to 0.7 SD lower mean areal bone mineral density Z‐score than girls with higher calcium intake and/or higher 25(OH)D status. The adverse association between lumbar spine mineralization and combined calcium deficiency–low 25(OH)D levels remained significant in the 91 girls who could be followed over 4 years after their initial evaluation. We conclude that low 25(OH)D levels (≤40 nmol/L) are observed frequently during winter–spring in late‐pubertal European girls, which may exacerbate the negative impact of calcium deficiency on lumbar spine mineralization. © 2010 American Society for Bone and Mineral Research.     

Long‐term outcome of pediatric renal transplantation: a single center experience

Abe T, Ichimaru N, Kakuta Y, Okumi M, Imamura R, Isaka Y, Takahara S, Kokado Y, Okuyama A. Long‐term outcome of pediatric renal transplantation: a single center experience.
Clin Transplant 2011: 25: 388–394. © 2010 John Wiley & Sons A/S. Abstract: Renal transplantation is the optimal treatment for pediatric end‐stage renal disease. We examined 51 children <20 yr old who underwent a total of 52 living‐donor renal transplantations at Osaka University Hospital between 1972 and 2004. The mean age at transplantation was 13.7 (3–19 yr). The mean duration of follow‐up was 16.5 yr. The five‐, 10‐, and 20‐yr patient survival rates following renal transplantation were 94%, 90%, and 87%, respectively. The five‐, 10‐, and 20‐yr graft survival rates were 76%, 65%, and 48%, respectively. A double‐drug regimen was used before 1987; this was replaced by a triple‐drug regimen including a calcineurin inhibitor in 1988. The five‐, 10‐, and 20‐yr graft survival rates after 1988 (89%, 80%, and 60%, respectively) were higher than those before 1987. Growth was examined among patients <15 yr old at the time of surgery, and height standard deviation (SD) scores (Z‐scores) were analyzed in 14 patients who displayed favorable renal function after transplantation. At the time of transplantation, mean SD score (SDS) was ?2.39, and mean final adult SDS was ?1.79. Rates of patient and graft survival after renal transplantation were mostly favorable. Future goals must include overcoming chronic rejection and establishing a steroid discontinuation protocol to improve growth.     

The effect of calcium intake and physical activity on bone quantitative ultrasound measurements in children: a pilot study

Environmental factors, such as nutritional status, physical activity, and drug therapy, can affect bone mineralization. Our objective was to evaluate the relationship between nutritional status, physical activity, and bone mineralization as assessed by multisite quantitative ultrasound technology in children. The study group comprised 67 children, aged 6–17 years (mean, 9.4), attending a primary care clinic. Data on calcium intake and physical activity were collected using a detailed questionnaire. Speed of sound measurements were performed at the distal 1/3 radius and the midshaft tibia using Sunlight Omnisense apparatus. The reported mean calcium intake was 1105 mg/day. There was a significant difference in Z-scores at the radius and tibia between the low-and high-calcium-intake groups (P = 0.004, P = 0.035, respectively). A similar difference was found between the low-and normal-physical-activity groups (P = 0.015, P = 0.036, respectively). In this pilot study, a positive association was found between calcium intake, physical activity, and bone status, as assessed by the quantitative ultrasound technique.     

Interactions of interleukin-6 gene polymorphisms with calcium intake and physical activity on bone mass in pre-menarche Chinese girls

Summary  This study assessed independent associations and interactions of IL-6 promoter alleles (−174G/C and −634C/G), calcium intake and physical activity with bone mass among pre-menarche Chinese girls. The −634 CC carriers, greater calcium intake and physical activity were associated with better bone mass. The gene-bone association was more pronounced among girls with high physical activity or with low calcium intake. Introduction  The association between interleukin (IL)-6 promoter polymorphisms and bone mass remains in debate. This cross-sectional study examined the association between the IL-6 promoter alleles (−174G/C and −634C/G) and bone mass, and assessed if the association could be modified by calcium intake or physical activity in pre-menarche Chinese girls. Methods  Two-hundred and twenty-eight healthy pre-menarche girls aged 9–11 years were recruited from primary schools in Guangzhou, China by sending letters to parents. None of them had diseases or medications known to affect bone metabolism. The IL-6 promoter genotypes were determined by PCR-RFLP, and BMD and BMC at the total body, lumbar spine, total hip and femoral neck were measured by DXA. Calcium intake and physical activity were assessed by face-to-face questionnaire interview. Results  One hundred and seventy-six subjects completed the entire study. We did not detect gene polymorphism at the IL-6 −174G/C locus, all were GG homozygotes. The IL-6 −634C/G polymorphism was significantly associated with both BMD and BMC even after adjusting for age and weight. Girls with CC genotype had higher levels of BMC and BMD than G allele carriers (+8.3% for the total body BMC, and +2.9%, +5.8%, and +5.7% for BMDs at the total body, total hip, and femoral neck, respectively; P < 0.05). The favorable effect of physical activity on BMDs at the total hip and femoral neck was much more pronounced in CC carriers than in G allele carriers, and the CC genotype associated higher BMDs at the total hip and femoral neck were observed only in girls with high level physical activity (P for interactions = 0.036 and 0.021, adjusted for age and weight). Calcium had a more benefit to the total body BMC in G allele carriers than in CC carriers, and the G allele-associated lower total body BMC was found only in subjects with low calcium intake. Conclusion  The IL-6 −634C/G polymorphism was significantly associated with BMD and the association might be modified by calcium intake or physical activity in pre-menarche Chinese girls.     

Influence of the ratio of particulate autogenous bone graft/platelet‐rich plasma on bone healing in critical‐size defects: A histologic and histometric study in rat calvaria

The purpose of this study was to analyze histomorphometrically the influence of the ratio of particulate autogenous bone (AB) graft/platelet‐rich plasma (PRP) on bone healing in surgically created critical‐size defects (CSD) in rat calvaria. Fifty rats were divided into five groups: Group C (control), Group AB, Group AB/PRP‐50, Group AB/PRP‐100, and Group AB/PRP‐150. A 5‐mm diameter critical‐size defect was created in the calvarium of each animal. In Group C, the defect was filled by blood clot only. In Group AB, the defect was filled with 0.01 mL of AB graft. In Groups AB/PRP‐50, AB/PRP‐100, and AB/PRP‐150, the defects were filled with 0.01 mL of AB graft combined with 50, 100, and 150 µL of PRP, respectively. All animals were euthanized at 30 days postoperative. Histomorphometry, using image analysis software, and histology analyses were performed. New Bone Area (NBA) and the remaining bone graft particles area (RPA) were calculated as a percentage of the total area of the original defect. Percentage data were transformed into arccosine for analysis. No defect completely regenerated with bone. Group AB/PRP‐50 (41.78 ± 13.48%) had a significantly greater NBA than Groups C (19.29 ± 5.11%), AB (27.43 ± 10.90%) or AB/PRP‐150 (19.17 ± 8.45%) (p < 0.05). No significant differences were observed between groups AB/PRP‐50 and AB/PRP‐100 or among groups AB, AB/PRP‐100, and AB/PRP‐150 with regard to NBA (p > 0.05). Group AB/PRP‐150 (31.59 ± 3.22%) had a significantly greater RPA than Groups AB (19.09 ± 5.21%), AB/PRP‐50 (17.33 ± 4.43%), and AB/PRP‐100 (19.72 ± 3.62%) (p < 0.001). No significant differences were observed among groups AB, AB/PRP‐50, and AB/PRP‐100 with regard to RPA (p > 0.05). The ratio AB graft/PRP influences bone healing in surgically created CSD in rat calvaria. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:468–473, 2010     

Validation of a physical activity questionnaire to measure the effect of mechanical strain on bone mass

Most of the questionnaires available to estimate the daily physical activity levels of humans are based on measuring the intensity of these activities as multiples of resting metabolic rate (METs). Metabolic intensity of physical activities is the most important component for evaluating effects on cardiopulmonary fitness. However, animal studies have indicated that for effects on bone mass the intensity in terms of energy expenditure (metabolic component) of physical activities is less important than the intensity of mechanical strain in terms of the forces by the skeletal muscles and/or the ground reaction forces. The physical activity questionnaire (PAQ) used in the Amsterdam Growth and Health Longitudinal Study (AGAHLS) was applied to investigate the long-term effects of habitual physical activity patterns during youth on health and fitness in later adulthood. The PAQ estimates both the metabolic components of physical activities (METPA) and the mechanical components of physical activities (MECHPA). Longitudinal measurements of METPA and MECHPA were made in a young population of males and females ranging in age from 13 to 32 years. This enabled evaluation of the differential effects of physical activities during adolescence (13-16 years), young adulthood (21-28 years), and the total period of 15 years (age 13-28 years) on bone mineral density (BMD) of the lumbar spine, as measured by dual-energy X-ray absorptiometry (DXA) in males (n = 139) and females (n = 163) at a mean age of 32 years. The PAQ used in the AGAHLS during adolescence (13-16 years) and young adulthood (21-28 years) has the ability to measure the physical activity patterns of both genders, which are important for the development of bone mass at the adult age. MECHPA is more important than METPA. The highest coefficient of 0.33 (p < 0.01) was between MECHPA measured over the total period of 15 years (13-28 years) and lumbar BMD at age 32 years. Only during adolescence (12-16 years) was METPA more important with regard to lumbar BMD at age 32 years, with a beta of 0.21 (p < 0.01). The relative validity of the PAQ was established by comparing PAQ scores during four annual measurements in 200 boys and girls with two other objective measures of physical activity: movement counters (pedometers) and heart rate monitoring. These showed significant (p < 0.01) correlations in both genders, varying between 0.16 and 0.20. The small variation indicates, however, that all three instruments measure different aspects of physical activity. The results from the PAQ, with respect to MECHPA, validated in humans the results from animal studies in which bone adaptation during skeletal growth and development continuously adjust skeletal mass and architecture to changing mechanical stimuli caused by physical activity.     

Effects of sodium bicarbonate supplementation on axial and peripheral bone mass in rats on strenuous treadmill training exercise

We observed the effects of sodium bicarbonate supplement on bone mass in rats on strenuous treadmill training. Sixty female Wistar rats (93-days-old; mean initial weight 261 ± 16 g) were studied. One group of 15 rats was killed at the beginning of the experiments (basal control group), while another group of 15 rats was not manipulated (Exer−NaB−). Another group of 15 rats was exercised but did not receive sodium bicarbonate (Exer+NaB−), while the final group of 15 rats exercised and received sodium bicarbonate (Exer+NaB+) at a dose of 0.05 mg/kg/day, administered by esophageal catheter on exercise days. These rats were killed at the end of 11 weeks. Femoral and vertebral length, weight, and bone mineral content (BMC) and density (BMD) were measured. According to anova with the Tukey–Kramer test, femur length and weight, vertebral weight, femur BMC and BMD, vertebral BMC and BMD and the ratio between femur and vertebral BMC and final body weight, and plasma bicarbonate were lower in the basal control and Exer+NaB− groups than in the two other groups (P < 0.005–0.0001). Overall, there was a positive correlation between femur and vertebral BMC and femur BMC and length (P < 0.0001 for all). Only in the Exer+NaB− group was there a positive association between plasma bicarbonate levels and femur length (r = 0.78; P < 0.0005). Our study demonstrates the adverse effects of strenuous exercise on bone, and the usefulness of sodium bicarbonate supplements in preventing and minimized these effects. Received: May 1, 2000 / Accepted: August 11, 2000     

The reduction of physical activity reflects on the bone mass among young females: a follow-up study of 142 adolescent girls

Summary Maintenance of positive effects of physical activity on growing bone is unknown. Physical activity was associated with increased BMC and BMD in a 7-year follow-up with 142 adolescent girls. Marked reduction in physical activity had an unfavorable effect on bone measurements, which is an important finding when the prevention of osteoporosis is considered. Introduction Environmental factors influence quality and durability of bone. Physical activity, with high-impact weight bearing activity during puberty in particular, has been shown to have a beneficial effect on growing bone. Only few studies have been published on the maintenance of these effects. Methods At baseline, 142 girls aged 9–15 years participated in the present 7-year follow-up study. Growth and development, physical activity, and intakes of calcium and vitamin-D were recorded at intervals. BMC and BMD measurements were repeated using DXA. Based on the recording of physical activity during the follow-up measurements, the effect of the reduction in physical activity was examined with the bone measurements, and the measurements in the tertiles based on the amount of physical activity during the whole follow-up period were compared. Results Physical activity was positively associated with the development of BMC and BMD during the follow-up. The mean BMC of the lumbar spine increased 1.69 g (3%) (p = 0.021) more among those girls who maintained the physical activity level as compared with those who reduced it during last 4 years. In the femoral neck, the corresponding difference was 0.14 g (4.6%) (p = 0.015) between the same two groups of girls. The mean increases in BMC at lumbar spine and femoral neck were more substantial among those girls having the highest physical activity levels during the 7-year follow-up (46.7% and 22.6%) as compared with those having the lowest physical activity levels (43.3% and 17.4%, respectively). Conclusions The findings of the present study show that regular physical activity is valuable in preserving the peak bone mass acquired at puberty in particular. Many of the girls who markedly reduced their activity levels lost bone in their femoral neck prior to their 25th birthday.     

High-protein intake enhances the positive impact of physical activity on BMC in prepubertal boys.

In 232 healthy prepubertal boys, increased physical activity was associated with greater BMC at both axial and appendicular sites under high-protein intake. INTRODUCTION: Physical activity is an important lifestyle determinant of bone mineral mass acquisition. Its impact during childhood can be modulated by nutrition, particularly by protein and calcium intakes. We analyzed the relationship between physical activity levels and protein compared with calcium intake on BMC. MATERIALS AND METHODS: In 232 healthy prepubertal boys (age: 7.4 +/- 0.4 [SD] yr; standing height: 125.7 +/- 5.9 cm; body weight: 25.3 +/- 4.6 kg), physical activity and protein and calcium intakes were recorded. BMC was measured by DXA at the radial metaphysis, radial diaphysis, total radius, femoral neck, total hip, femoral diaphysis, and L(2)-L(4) vertebrae. RESULTS: In univariate analysis, the correlation coefficients r with BMC of the various skeletal sites were as follows: physical activity, from 0.26 (p = 0.0001) to 0.40 (p = 0.0001); protein intake, from 0.18 (p = 0.005) to 0.27 (p = 0.0001); calcium intake, from 0.09 (p = 0.181) to 0.17 (p = 0.007). By multiple regression analysis, the beta-adjusted values remained correlated with BMC, ranging as follows: physical activity, from 0.219 (p = 0.0007) to 0.340 (p < 0.0001); protein intake, from 0.120 (p = 0.146) to 0.217 (p = 0.009). In contrast, it was not correlated for calcium intake: from -0.069 (p = 0.410) to 0.001 (p = 0.986). With protein intake (mean = 2.0 g/kg body weight/d) above the median, increased physical activity from 168 to 321 kcal/d was associated with greater mean BMC Z-score (+0.6, p = 0.0005). In contrast with protein intake (mean = 1.5 g/kg body weight/d) below the median, increased physical activity from 167 to 312 kcal/d was not associated with a significantly greater mean BMC Z-score (+0.2, p = 0.371). The interaction between physical activity and protein intake was close to statistical significance for mean BMC Z-score (p = 0.055) and significant for femoral neck BMC (p = 0.012). In keeping with the results derived from multiple regression analysis, the increased physical activity on mean BMC Z-score was not influenced by difference in calcium intake above (mean = 945 mg/d) and below (mean = 555 mg/d) the median. CONCLUSION: In healthy prepubertal boys, the impact in increased physical activity on BMC seems to be enhanced by protein intake within limits above the usual recommended allowance.