J Bone Miner Res 2008 (May); 23 (5): 741–749 ~ FULL TEXT
Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson K
Creighton University Osteoporosis Research Center,
Omaha, Nebraska, USA
Are You Too Young To Supplement?
Commentary from Dr. Stephen Chaney, PhD
I constantly run into people who think that supplements
are just for the old and the sick.
These people say: "I'm young and healthy. Why should I
I came across a very interesting article that answers
This study showed that calcium and vitamin D
supplementation reduced the risk of stress fractures in
people who were very active.
Now you might be tempted to say "That's not news - but
doesn't that just apply to older people".
That's what made this article so interesting. This
study was performed on 5,201 female U.S. Navy recruits
- not exactly the geriatric set.
The women, ages 17 to 35, were divided into two groups
with one group receiving daily supplements containing
2,000 mg of calcium and 800 IU of vitamin D, and the
other group receiving placebo pills.
The study was conducted during eight weeks of basic
training from 2002 to 2006 at Great Lakes Naval Station
near Chicago, IL.
During the study, 170 recruits in the placebo group
experienced stress fractures, about 25 percent more
than in the group taking the calcium/vitamin D
The scientists in charge of the study said "What really
surprised us is that calcium/vitamin D supplements made
a significant difference in such a short period of
time. Frankly, we were not sure we would see any
statistically significant results in only eight weeks."
The implications of this study are enormous.
Stress fractures are one of the most common and
debilitating overuse injuries seen in U.S. military
recruits in all branches of the Armed Forces. Estimates
are that as many as 21 percent of all female recruits
suffer this injury.
Stress fractures often lead to chronic pain and
disability. In addition, the cost of a single soldier
discharged from basic training is estimated to be
$34,000, not including expenses related to health care.
More importantly, the scientist running the study
pointed out that the same results would probably be
seen in anyone who was physically active at any age.
For example, the study may also have implications for
nonmilitary athletic populations, such as high school
track and field athletes, in whom stress fractures also
The lead investigator concluded: "It appears that
supplementation with calcium and vitamin D provides a
health-promoting, easy and inexpensive intervention
that does not interfere with training goals."
So are you too young for supplementation? I don't think
Dr. Stephen Chaney, PhD
Professor at University of North Carolina at Chapel Hill School of Medicine
INTRODUCTION: Stress fractures (SFx) are one of the most common and debilitating overuse injuries seen in military recruits, and they are also problematic for nonmilitary athletic populations. The goal of this randomized double–blind, placebo–controlled study was to determine whether a calcium and vitamin D intervention could reduce the incidence of SFx in female recruits during basic training.
MATERIALS AND METHODS: We recruited 5201 female Navy recruit volunteers and randomized them to 2000 mg calcium and 800 IU vitamin D/d or placebo. SFx were ascertained when recruits reported to the Great Lakes clinic with symptoms. All SFx were confirmed with radiography or technetium scan according to the usual Navy protocol.
RESULTS: A total of 309 subjects were diagnosed with a SFx resulting in an incidence of 5.9% per 8 wk. Using intention–to–treat analysis by including all enrolled subjects, we found that the calcium and vitamin D group had a 20% lower incidence of SFx than the control group (5.3% versus 6.6%, respectively, p = 0.0026 for Fisher's exact test). The per protocol analysis, including only the 3700 recruits who completed the study, found a 21% lower incidence of fractures in the supplemented versus the control group (6.8% versus 8.6%, respectively, p = 0.02 for Fisher's exact test).
CONCLUSIONS: Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the 24 mo of recruitment, calcium and vitamin D supplementation for the entire cohort would have prevented approximately 187 persons from fracturing. Such a decrease in SFx would be associated with a significant decrease in morbidity and financial costs.
From the FULL TEXT Article:
Physical training and exercise during early adulthood is known to increase bone strength. [1–4] Therefore, intense training for young athletes or military recruits provides an opportunity to maximize bone strength or resistance to fracture. Paradoxically, prolonged intensive training can result in fatigue damage and stress fractures. Stress fractures are among the most common and debilitating overuse injuries seen in military recruits, with fracture rates ranging from 0.2% to 5.2% of male recruits and 1.6% to 21.0% of female recruits. [5–10] Stress fracture rates for female recruits are consistently higher than for men. Stress fractures are also problematic for nonmilitary athletic populations. The highest incidence rates, ranging from 10% to 31%, are seen in members of track and field teams. [8, 11–13]
Stress fractures occur when bones are repetitively loaded over short periods without sufficient time for repair and are seen most often among persons who are involved in physical activity to which they are not adapted. Stress fractures are a major concern for the armed forces because they result in morbidity ranging from pain to permanent disability. In addition, these injuries incur considerable expense for the military. At one U.S. Army training base, recent estimates were that over the span of 1 yr, $26 million was lost in training costs for the 749 soldiers who were discharged from training, an average of more than $34,000 per soldier.  In the U.S. Army, 40% of men and 60% of women trainees with stress fracture do not complete basic training. Thus, stress fractures also negatively affect military readiness.
In recent years, the U.S. Military Services have decreased the incidence of stress fractures in recruits by making changes to basic training. At the Great Lakes Naval Station, these changes included different types of boots and training shoes, strict guidelines for physical training (PT), and shorter stride lengths while marching in formation. Although these training guidelines have reduced stress fractures, a significant number of fractures still occur. The remaining fractures may be caused by high risk at entry associated with genetic or lifestyle factors or poor skeletal adaptation to physical training.
Numerous studies have found genetic or lifestyle factors that significantly predict stress fracture. [7, 8, 15–17] However, for the most part, the predictor variables have low sensitivity and specificity. Although these and other risk factors may be useful for identification of modifiable variables, they are not useful for identifying individual recruits at highest risk for stress fracture. Thus, the military has no accurate method of selecting individual recruits to target for stress fracture prevention. Because prevention programs add cost to training, the military services are reluctant to implement such programs unless they can be highly targeted. Alternatively, interventions that can safely and effectively be applied to all recruits are desirable.
Strong rationale exists for a calcium and vitamin D intervention in Navy recruits and other similar groups. Calcium is essential for bone mineralization, and a positive calcium balance is necessary for maximal bone adaptation to mechanical loading.
There are five primary reasons that calcium and vitamin D supplementation may be important for young women during basic military training:
women <30 yr of age have not achieved peak bone mass and have the potential to gain bone, which requires that they be in positive calcium balance
intense training stimulates bone formation, increasing calcium demands
microfracture repair through remodeling requires calcium for bone formation
substantial cutaneous calcium losses can occur during training
calcium and vitamin D nutrition of young women is typically less than optimal.
Calcium and vitamin D supplementation is widely used to prevent osteoporotic fractures in older individuals, and it is safe and generally well tolerated. Thus, the goal of this study was to determine whether a calcium and vitamin D intervention could reduce the incidence of stress fractures in female recruits during basic training.
To our knowledge, this is the first randomized controlled trial of the efficacy of calcium and vitamin D supplementation that has shown a decreased incidence of stress fracture. Schwellnus and Jordaan  studied the effect of calcium supplementation in preventing stress fractures in male military recruits in South Africa but found no statistically significant effect. That study was underpowered because the sample size included only 250 recruits given supplementation, and the calcium supplementation was low (500 mg/d). Only 14 stress fractures were diagnosed over the 9–wk training period (incidence of 1.4% in the control group and 0.64% in the supplement group).
It is well established that adequate calcium nutrition is essential for skeletal strength. When serum calcium levels fall because of insufficient intake or excessive loss of calcium, PTH production is increased to stimulate bone resorption and liberate calcium from the skeleton to restore serum calcium concentration. [30, 31] This has been called nontargeted (stochastic) remodeling [22, 23] and can persist over extended periods of time, as long as the stress to plasma calcium persists. The bone response to the increased PTH is to increase the rate of activation of new remodeling sites, thus increasing the remodeling space. This results in an imbalance of bone remodeling in which more bone is lost from the skeleton than is replaced, and skeletal strength is compromised. Under conditions of intense mechanical loading, such as occurs during basic military training, microfractures develop and lead to targeted remodeling to repair the microfractures. [22, 23, 32] In this situation, optimal levels of circulating calcium are needed to provide substrate for repair of microdamage and to inhibit an increase of nontargeted remodeling to maintain serum calcium concentration.
High levels of physical activity in the presence of low (or even moderately plentiful) calcium intake can cause additional stress on the skeleton because of the need to offset the substantial cutaneous calcium loss in the sweat. Under conditions of heavy sweating and insufficient calcium intake, calcium is drawn from the bone reservoir under the influence of elevated levels of PTH. In fact, acute bouts of exercise increase PTH levels proportional to exercise intensity. [30, 33–36] The cutaneous calcium losses during heavy physical activity can be substantial, [24–26] and the resultant secondary hyperparathyroidism can weaken the skeleton even over short periods. In that regard, Thorsen et al.  reported that young women showed increased bone turnover, decreased serum ionized calcium, and increased serum PTH after a single bout of moderate endurance exercise. This calcium stress may act to limit skeletal adaptation and repair mechanisms in both military recruits and athletes during strenuous activity.
Klesges et al.  measured cutaneous calcium loss in 11 members of the University of Memphis' men's basketball team during a 10–day training period. Cutaneous calcium loss averaged 422 mg per each 2–h training session. Average total body BMC decreased by 3.8% from preseason to midseason (p = 0.02), a period of 4 mo, whereas leg bone mass decreased 6% (p = 0.01). From preseason to late summer, the players lost 6.1% of their total BMC and 10.5% of their leg bone mass (p = 0.001 and p < 0.001, respectively). Individual players lost as much as 20.2% of their leg bone mass during this 10.5–mo interval. During year 2 of the study, the athletes were supplemented with calcium and vitamin D at doses based on each individual's BMC loss in year 1. Supplementation not only stopped losses in BMC, but increased total BMC by almost 2% and leg BMC by 3% by midseason of year 2 (p = 0.04 and 0.05, respectively). This study showed that sweat loss contributes to a considerable loss of BMC in young men who should not be losing bone. Furthermore, sufficient dietary calcium can offset cutaneous losses and allow adequate bone adaptation. The bone loss and subsequent gain with supplementation in the study of Kleges et al. were seen over a relatively short period of time, ~4 mo. In our study at the Great Lakes, supplementation prevented stress fracture over ~2 mo.
Although no studies were found using vitamin D supplementation to decrease stress fracture incidence, Ruohola et al.  found that low baseline 25 hydroxyvitamin D [25(OH)D] predicted stress fracture in Finnish male military recruits. In that study, 800 randomly selected recruits (mean age, 19 yr) were followed prospectively over 90 days, which included 8 wk of basic training. Twenty–two recruits with stress fracture were identified (2.9%). In the final multivariate analysis, a significant risk factor for stress fracture was serum 25(OH)D below the median level of 75.8 nM (OR = 3.9; 95% CI = 1.2–11.1; p = 0.002). It is well established that a small reduction in vitamin D status can contribute to mild increase in PTH concentration because vitamin D, in the form of 1,25 dihydroxyvitamin D, regulates the active transport mechanism of calcium absorption from the gut. [38, 39] Bone turnover increases in response to the elevated serum PTH levels. An earlier study of Finnish male recruits  found that high serum PTH levels were associated with stress fracture. These reports support our finding that supplementation with vitamin D can decrease stress fracture incidence.
Supplementation with calcium and vitamin D significantly reduced the risk of stress fracture overall despite the negative effects of several lifestyle factors. The supplementation was well tolerated. In fact, the percent of subjects withdrawing from study because of adverse events was 4% in each of the groups (placebo and treatment). These findings lend confidence that supplementation with calcium and vitamin D is a viable option to for preventing stress fractures, even in populations with factors that significantly increase the risk of fracture.
It is important to note that several factors increase the risk of stress fracture in these female recruits despite treatment: amenorrhea during training, age > 25 yr, and history of smoking, low levels of physical activity, and Depo use. Also, those who were less physically fit at the beginning of training had a higher risk of fracture than their more fit counterparts.
Poor physical fitness is widely reported to be associated with stress fracture. [8, 9, 40–42] In our earlier study of female Army recruits,  we found that nonexercisers in the lowest quintile of quantitative ultrasound speed of sound (SOS) had nearly a nine times greater risk of fracture than did nonexercisers in the highest quintile. Thus, strong evidence supports the importance of pretraining activities to improve the fitness of young women gradually before initiating intense physical activity programs. In our Naval study, it is interesting to note that, within the placebo group, the high exercise group had a 34% lower risk of stress fracture than the low exercise group, whereas this exercise history effect was not seen in the supplemented group. Numerous studies of military recruits have found that a history of regular physical activity decreases risk of stress fracture. [7–9, 16] Our findings suggest that calcium/D supplementation can somewhat compensate for a history of low physical activity, which is prevalent in U.S. youth, [43, 44] the group entering the military services.
Although supplementation lowered the risk somewhat, recruits with a history of smoking still had a 41% higher risk of fracture than those who had never smoked. Other researchers have reported that smoking increases risk of stress fracture. [15, 45, 46] Furthermore, numerous investigators have reported an inverse relationship between BMD and smoking. [47–51] In our previous study,  we found that female recruits in the lower quintile of SOS who did not exercise and smoked had a risk of fracture nearly 12 times greater than those with higher SOS values who exercised and did not smoke. Krall and Dawson–Hughes  reported that smokers lost bone more rapidly than nonsmokers and had significantly lower calcium absorption, suggesting that poor absorption of calcium may contribute to the faster rate of bone loss. In a meta–analysis of the effects of cigarette smoking on bone, Ward and Kleges  found that smokers had significantly lower bone mass than nonsmokers at all skeletal sites, and the difference was dose dependent. Thus, history of smoking in female recruits should serve as a “red flag” indicating high risk of sustaining a stress fracture during basic training.
As we found in an earlier study at a U.S. Army training base,  women who had a history of using the long–acting progesterone contraceptive, Depo, had a higher risk of fracture than those who had not used Depo. Similar to other stress fracture studies, [8, 9, 46] women at the Great Lakes who reported no menses during basic training had a significantly greater risk of stress fracture than those with one or more menstrual periods. This risk remained significant when controlled for Depo use and treatment group. Absence of menses, whether because of Depo use or other causes, is a reflection of very low circulating estrogen levels, which are associated with lower bone mass [54, 55] and higher risk of fracture. [56, 57]
On average, the Navy recruits in our study had suboptimal calcium intake: 300 mg/d compared with the recommended 1000 mg/d for young women. Thus, it is not surprising that calcium supplementation reduced their risk of stress fracture. As would be expected, our study showed that young women enter basic military training with a variety of risk factors for stress fractures in addition to low calcium intake, such as smoking history, use of progesterone contraceptives, poor physical fitness, etc. The effect of calcium and vitamin D supplementation was strong even when adjusting for these factors. Thus, it seems prudent to provide supplementation to all female recruits.
The incidence of stress fracture in our cohort of young women was 5.9%. This is lower than other reports and may reflect the successful efforts of the Navy to change the skeletal demands of basic training. Our study shows that supplementation with calcium and vitamin D can provide additional benefits to the successful training changes that have already been implemented by the armed forces.
Although there were only 11 fractures of the pelvis and pubis, there were more than twice as many in the placebo group as in the calcium and vitamin D group. The difference between treatment groups was not statistically significant because of the small numbers of fractures. However, the difference is medically significant considering the morbidity and potential disability, as well as the medical treatment costs, associated with fractures at these sites.
One limitation of this study was that 1136 (21.8%) of the subjects withdrew from the study. However, ~7% of those withdrew so that they could take calcium and vitamin D supplementation provided by Great Lakes medical caregivers and not risk being on placebo. Discounting that group, the attrition is 20%, which is congruent with many clinical trials.
In conclusion, calcium and vitamin D substantially reduced the incidence of stress fractures by 20% in female Naval recruits in this study. Generalizing the findings to the population of 14,416 women who entered basic training at the Great Lakes during the study period, calcium and vitamin D supplementation for the entire cohort would have prevented ~187 persons from fracturing. Such a decrease in stress fracture would be associated with a significant decrease in morbidity and financial costs. Supplementation with calcium and vitamin D provides a safe, easy, and inexpensive intervention that does not interfere with training goals.