Ville-Valtteri Välimäki, Henrik Alfthan, Eero Lehmuskallio, Eliisa Löyttyniemi, Timo Sahi, Ulf-Håkan Stenman, Harri Suominen, Matti J. Välimäki, Vitamin D Standing as a Determinant of Peak Bone Mass in Younger Finnish Males, The Journal of Medical Endocrinology & Metabolism, Quantity 89, Difficulty 1, 1 January 2004, Pages 76–80, https://doi.org/10.1210/jc.2003-030817
SEVERE VITAMIN D deficiency causes rickets and osteomalacia, whereas milder hypovitaminosis contributes to the event of osteoporosis. In Finland, vitamin D supplementation is really useful to infants from the age of two wk to three yr (beforehand 2 yr) to forestall rickets and to aged individuals for prophylaxis of osteoporosis. After the prevention of rickets in infancy, much less consideration has been paid to the function of vitamin D within the building-up of peak bone mass in rising youngsters and younger adults. This has been the case regardless of alarming findings of the poor vitamin D state of younger individuals in Finland and different international locations. Three of 4 Finnish women, aged 9–15 yr, had average hypovitaminosis D [serum 25-hydroxyvitamin D (25-OHD), ≤37.5 nmol/liter] within the winter of 1997 (1). Within the winter, 70% of French boys, aged 13–16 yr, had serum 25-OHD concentrations lower than 25 nmol/liter (2). In a Finnish research, stopping vitamin D supplementation after infancy clearly resulted in a rise within the prevalence of extreme hypovitaminosis D (serum 25-OHD, ≤12.5 nmol/liter), from 7.5% in youngsters 2–5 yr of age to 23.5% within the 11–17 yr age group (3).
Though adolescence is a vital time for bone well being, the connection in younger individuals between vitamin D standing, outlined by serum 25-OHD measurements, and bone mass has been addressed in solely two research (4, 5). A weak affiliation between forearm bone mineral density (BMD) and serum 25-OHD concentrations was present in Finnish feminine adolescents, aged 14–16 yr; backbone or hip measurements weren’t carried out (4). In a really latest follow-up research of 171 Finnish women, aged 9–15 yr, the adjusted 3-yr enhance in lumbar backbone BMD was higher, the upper the serum 25-OHD degree at baseline (5).
The current research was undertaken to look at vitamin D standing of younger Finnish males and its impression on peak bone mass measured within the lumbar backbone and the higher femur by twin power x-ray absorptiometry. The seasonal variation in serum 25-OHD concentrations was additionally adopted, and it was associated to modifications in serum intact PTH (iPTH) concentrations and bone turnover markers.
Topics and Strategies
The research inhabitants comprised 220 younger males, aged 18.3–20.6 yr. They had been members in a research aimed toward elucidating the roles of genes, hormones, and life-style elements as determinants of peak bone mass and finding out exercise-induced modifications in bone mass throughout navy service. 100 and seventy males had been recruits of the Finnish Military, and 50 topics, males of comparable age who had postponed their navy service for causes unrelated to well being, fashioned a management group for the train a part of the research. For the aim of the current research, the two teams had been mixed. The research was accepted by the moral committee of Division of Drugs, Helsinki College Central Hospital, and a written consent was obtained from the members.
Research design
Each teams had been at all times examined on the similar time. They had been first studied throughout early July 2000 firstly of the navy service of the recruits. BMD was measured, and blood was sampled within the morning earlier than 1000 h for dedication of serum 25-OHD, iPTH, sort I procollagen amino-terminal propeptide (PINP), and tartrate-resistant acid phosphatase 5b (TRAP5b). Second-void urine samples had been collected for the dedication of sort I collagen amino-terminal telopeptide (NTX). The samples had been saved at -70C till assayed.
Present train, smoking, calcium consumption, and alcohol consumption had been recorded utilizing a questionnaire. To review the seasonal variation in serum 25-OHD concentrations and different biochemical parameters, blood and urine sampling was repeated after 6 and 12 months. Altogether 167 males had been studied at 6 months, and 94 males had been studied at 12 months. The primary motive for the lower within the variety of males studied was the length of the navy service, which in Finland varies from 6–12 months.
Train
The participation in numerous bodily actions over the past yr was recorded at baseline utilizing a questionnaire. The questions used for the aim of this report included 30 various kinds of bodily exercise and coaching, which had been weighted in response to their bone loading impact. Gentle or nonweight-bearing actions, comparable to strolling, biking, and swimming, scored 1; actions producing repetitive weight-bearing impression (e.g. endurance operating and snowboarding) scored 1.5; and excessive impression or excessive magnitude loading (e.g. leaping, dash operating, and weight-lifting) scored 2. For every sort of train practiced, the themes had been requested to point the typical variety of events per 30 days and the length (minutes) and depth (1 = gentle, 2 = average, 3 = heavy) of every event. An train index was then calculated by summing up the merchandise of frequency, length, depth, and bone loading impact of various actions in summer time and wintertime.
Calcium consumption
Calcium consumption was calculated on the idea of the availability from dairy merchandise solely through the use of the next estimations: 1 dl milk, bitter milk, and yogurt comprises 120 mg calcium, and one slice of cheese comprises 100 mg. Within the calculations 1.8 dl was used as the amount of 1 glass.
Biochemical measurements
Serum 25-OHD was measured by RIA kits from Diasorin (Stillwater, MN). At vitamin D ranges of 30 and 100 nmol/liter, the intraassay coefficients of variation (CVs) had been 8.9% and 5.9%, and the interassay CVs had been 12.8% and eight.8%, respectively. Serum iPTH was assayed utilizing intact PTH kits from Diagnostics Merchandise Corp. (Los Angeles, CA) and the IMMULITE 2000 immunoassay analyzer. At ranges of twenty-two and 38 ng/liter, the intraassay CVs had been 4.3% and 4.2%, and the interassay CVs had been 5.3% on the degree of 68 ng/liter and three.4% on the degree of 366 ng/liter. Urinary NTX was measured with NTX reagent kits (Amersham Pharmacia Biotech, Little Chalfont, UK) on the Vitros Eci Immunodiagnostics Methods analyzer (Ortho-Medical Diagnostics, Inc., Rochester, NY). The intraassay CV was 8.0% on the degree of 55 nm bone collagen equivalents (BCE)/liter and three.0% on the degree of 187 nm BCE/liter. The interassay CV was 9.8% on the degree of 60 nm BCE/liter and 5.3% on the degree of 403 nm BCE/liter. The values had been corrected for creatinine excretion measured by an ordinary laboratory methodology. Serum intact PINP was decided by a aggressive RIA with a business package (Intact PINP RIA) from Orion Diagnostica (Oulunsalo, Finland). The analytical sensitivity of this assay was 2 μg/liter, and the intra- and interassay CVs ranged from 2–6%. Serum TRAP5b exercise was measured by an immunoextraction methodology with BoneTRAP reagents from Suomen Bioanalytiikka Oy (Turku, Finland) (6). The analytical sensitivity of this assay was 0.1 U/liter, and the intra- and interassay CVs had been 6% or much less at related concentrations.
Vitamin D deficiency
Vitamin D deficiency was outlined as a worth decrease than the decrease restrict of the Finnish reference vary (20–105 nmol/liter) of serum 25-OHD focus.
Bone mass measurements
Bone mineral content material (BMC) and BMD of the lumbar backbone and three femoral websites (femoral neck, trochanter, and whole hip) was measured by twin power x-ray absorptiometry utilizing a Prodigy densitometer (Lunar Corp., Madison, WI). The scan areas of the lumbar backbone and the femoral neck had been additionally taken into consideration within the calculations.
Statistics
Baseline BMC, BMD, and scan space values had been analyzed utilizing a a number of regression mannequin by adjusting for age, peak, weight, calcium consumption, smoking, alcohol consumption, train, and biochemical marker (separate mannequin for every marker). As well as, Pearson correlation was calculated between BMC and biochemical markers. The research inhabitants was divided into two classes based mostly on the median worth of serum 25-OHD at baseline (=44 nmol/liter), after which these above and under the median had been in contrast with respect to bone mass variables and biochemical markers utilizing one-way ANOVA. The modifications over time in biochemical markers had been analyzed utilizing repeated measures ANOVA. For all biochemical markers, pure logarithm transformation was used to realize normality assumption within the fashions. All checks had been carried out as two-sided, with a 0.05 significance degree. All analyses had been carried out with the SAS system (model 8.02 for Home windows, SAS Institute, Inc., Cary, NC).
Outcomes
The baseline traits of the research inhabitants are given in Desk 1.
Prevalence of vitamin D deficiency
At first of the research in July 2000, 2 of 220 males (0.9%) had serum 25-OHD lower than 20 nmol/liter. Six months later within the winter, the corresponding proportion was 38.9% (65 of 167 males), and throughout the subsequent summer time it was 2.1% (2 of 94 males). The median ranges of serum 25-OHD had been 44, 24, and 41 nmol/liter, respectively.
Determinants of bone mass
In Desk 2 lumbar backbone and femoral neck BMC, BMD, and the respective scan areas in addition to trochanteric and whole hip BMC and BMD are associated to anthropometric and life-style elements and vitamin D standing in a a number of regression mannequin. Present train (P < 0.0001) and weight (P < 0.0001–0.13) correlated most constantly with the BMCs studied. Resulting from its very slender vary, age was a determinant just for lumbar backbone BMC. Calcium consumption was not a determinant of BMC, however was of borderline significance for BMD within the femoral neck, trochanter, and whole hip. Smoking historical past and alcohol consumption didn't have any relationship to bone mass. Apparently, the serum 25-OHD focus was a determinant of BMC in any respect 4 measurement websites, the P values being 0.057 for lumbar backbone, 0.041 for femoral neck, 0.010 for trochanter, and 0.025 for whole hip BMC. The correlation coefficients to the BMDs had been 0.035, 0.061, 0.056, and 0.068, respectively. No correlation was discovered between serum 25-OHD and scan space. Unadjusted Pearson correlation coefficients (r values) between 25-OHD and BMCs had been between 0.17 and 0.24, with the respective P values starting from 0.0005–0.013 (Desk 3).
Bone mass and biochemical parameters under and above the median of serum 25-OHD At baseline the median degree for serum 25(OH)D was 44 nmol/liter. These above this degree had the next BMC within the trochanter (P = 0.015) and whole hip (P = 0.037) than these under the median (Desk 4). Serum iPTH was greater (P = 0.058) in these under than above the median serum 25-OHD. Correlations between biochemical parameters at baseline Serum 25-OHD correlated negatively with serum iPTH (r = −0.24; P = 0.0007), however we couldn't discover any threshold degree for serum 25-OHD at which serum iPTH would have began to rise. Serum 25-OHD correlated positively with serum TRAP5b (r = 0.17; P = 0.012). Urinary NTX, serum TRAP5b, and PINP correlated with one another (r = 0.45–0.52; P < 0.0001). Serum 25-OHD was not depending on smoking historical past (r = −0.11; P = 0.11), and serum iPTH was not related to calcium consumption (r = −0.08; P = 0.26). Seasonal variation in biochemical markers As offered above, serum 25-OHD exhibited an anticipated seasonal variation, with a nadir within the winter (P < 0.0001; Desk 5). Serum iPTH confirmed inverse modifications over time (P = 0.0001), with a most within the winter, however the magnitude of this variation was smaller than that of vitamin D (Desk 5). Urinary excretion of NTX (P < 0.0001) and serum TRAP5b (P < 0.0001) and PINP (P = 0.0002) concentrations declined over time, with a nadir on the finish of the research (Desk 5).Dialogue
The primary findings of the current research had been that amongst younger Finnish males vitamin D deficiency is quite common throughout the winter, and vitamin D standing is a determinant of peak bone mass in male adolescents.
We outlined vitamin D deficiency as values decrease than the decrease restrict of the Finnish reference vary, however a number of totally different definitions might be discovered for vitamin D deficiency and hypovitaminosis D within the literature. Thomas et al. (7) outlined hypovitaminosis D as the extent of serum 25-OHD at which serum iPTH concentrations began to extend. Of their research the extent was 37.5 nmol/liter, however this threshold varies with totally different research. In our earlier research of middle-aged and aged Finnish individuals, a dramatic rise in serum iPTH occurred when serum 25-OHD concentrations fell under 12.5 nmol/liter, though a big rise was noticed under a degree of fifty nmol/liter (8). In a French grownup inhabitants, serum iPTH ranges started to extend already when serum 25-OHD fell under 78 nmol/liter (9). Though serum 25-OHD and iPTH concentrations correlated negatively within the current research inhabitants, we weren’t capable of decide a definite threshold for the PTH rise. That is appropriate with a latest discovering displaying that for comparable 25-OHD concentrations, PTH concentrations are constantly greater within the aged than in youthful adults (10). Hypovitaminosis D has additionally been outlined as the brink above which there was no enhance in serum iPTH values throughout the winter; in a single research the rise disappeared on the degree of 95 nmol/liter (11). Moreover, calcium absorptive efficiency at 50 nmol/liter was considerably decreased relative to that at a imply 25-OHD degree of 86 nmol/liter, which means that people with serum 25-OHD ranges on the low finish of the present reference vary is probably not getting the complete profit from their calcium consumption (12). Lastly, amongst individuals aged 65 yr or extra, rising a imply 25-OHD degree from 53 to 74 nmol/liter by supplementation decreased fracture danger at hip, forearm, and backbone by 33% in 5 yr (13). Independently of the definition used for adequate vitamin D state, the median ranges of 24 nmol/liter within the winter and 41–44 nmol/liter throughout the summer time had been low in our research inhabitants. Nonetheless, when defining hypovitaminosis D in absolute phrases of serum concentrations of 25-OHD, it must be taken into consideration that the values from totally different laboratories can’t be assumed to be comparable until a cautious cross-calibration has been carried out (14).
To our data that is the primary report to point out that vitamin D standing contributes to peak bone mass in male adolescents. Our research inhabitants consisted of males aged 18.3–20.6 yr, by which age peak bone mass has been achieved; in a research by Bonjour et al. (15), bone accretion within the lumbar backbone and femoral neck was accomplished in males at 17–18 yr of age. Serum 25-OHD concentrations correlated positively with BMC within the lumbar backbone and the three measurement websites of the higher femur additionally after adjusting for anthropometric and life-style elements in a a number of regression mannequin. For 2 femoral websites, the BMC was greater for these with a serum 25-OHD focus above its median of 44 nmol/liter than for these with ranges under this cut-off worth. The truth that BMC, however not scan space (and, accordingly, bone dimension), correlated with serum 25-OHD favors the concept in rising youngsters and adolescents vitamin D will increase mineral accretion quite than bone dimension, and consequently, true density additionally will increase.
Serum 25-OHD concentrations as a determinant of peak bone mass has not been studied in younger males, however the relationship has been addressed in feminine adolescents in two research. Amongst 178 Finnish women, aged 14–16 yr, ulnar and radial BMDs adjusted for train had been barely decrease in these with serum 25-OHD of 40 nmol/liter or lower than in these above this cut-off degree (4). In one other research, amongst 171 Finnish women, aged 9–15 yr, the adjusted 3-yr accumulation from baseline in lumbar backbone BMD was 4% smaller in these with serum 25-OHD ranges under 20 nmol/liter than in these with serum 25-OHD exceeding 37.5 nmol/liter (5). Two earlier research present oblique proof for a relationship between vitamin D standing and peak bone mass. Inadequate vitamin D consumption was thought of as one rationalization for decreased bone mass in Dutch adolescents, aged 9–15 yr, who had been fed a macrobiotic food regimen in youth; the discount as compared with controls couldn’t be attributed to group variations in calcium consumption or bodily exercise (16). In 371 topics, aged 20–23 yr, amongst different elements, forearm BMD was positively related to vitamin D consumption throughout adolescence (17).
Our research confirmed the function of train as a very powerful life-style think about reaching a excessive peak bone mass (18–20). Calcium consumption had a borderline optimistic impact on BMD of the higher femur, which is in accordance with earlier findings (21). We weren’t capable of affirm our earlier findings of a unfavourable impact of smoking on bone mass in males aged 20–29 yr (20). The variations in age and consequently within the size of smoking historical past most clearly defined the discrepancy between the two research. Smoking was additionally not negatively related to serum 25-OHD focus, which was the case in a research of 328 Finnish adults, aged 31–43 yr (22).
Serum iPTH correlated negatively with 25-OHD at baseline, and it additionally confirmed a seasonal variation that was inverse to however in magnitude smaller than that in vitamin D. Serum calcium and phosphate concentrations are the primary determinants of serum iPTH, however its regulation is multifactorial (22). We examined the dependency of serum iPTH on calcium consumption, however no affiliation was discovered on this research inhabitants. At baseline, serum iPTH didn’t correlate with markers of bone resorption, urinary NTX and serum TRAP5b, or a marker of bone formation, serum PINP. The rise in iPTH focus throughout the winter was additionally not mirrored in a rise in bone markers. As a substitute, the entire markers confirmed a declining development over the entire research interval, which is defined by the completion of development in our topics. In boys, bone markers are at their most in pubertal stage G4, decline thereafter, relate on to peak velocity, and are optimistic predictors of achieve in bone mass (23). All of those biochemical findings favor the concept on this age group vitamin D will increase bone accretion quite straight than by suppressing bone resorption via lowered iPTH ranges.
In conclusion, vitamin D deficiency is quite common in Finnish younger males throughout the winter, and it could have detrimental results on the acquisition of maximal peak bone mass. The outcomes strongly favor intervention research on the results of vitamin D supplementation on the rising skeleton. Our outcomes additionally raises the query of whether or not at Finland’s latitude vitamin D supplementation needs to be continued past 3 yr of age, not for the prevention of rickets however as a prophylaxis for osteoporosis. This suggestion is additional supported by a latest discovering of an affiliation between poor vitamin D consumption and excessive incidence of sort I diabetes in Finland (24).
This work was supported by a grant from the Ministry of Schooling (Helsinki, Finland) and analysis funding from Helsinki College Central Hospital (Erityisvaltionosuus).
Abbreviations:
– “vitamin d peak”
“vitamin d peak”