Bones

Imagine where you would be without your bones. Bones let you flex your muscles, bones help you win races, bones let you climb mountains, and bones make you taller than a sibling, among other things. You want healthy bones that work well over a lifetime.

With that in mind, this is a brief review of bones, how you grow them, how you maintain them, and how important diet and nutrients are to your bone health, to be sure they last that lifetime.

Bone is primarily made up of two components, an organic part, and a mineral part. The organic part is comprised of collagenous and non-collagenous proteins (30%) and cells. Collagen is a type of protein, and it is the most abundant protein in the body, representing more than 90% of the organic matrix. Its fiber-like structure is used to make connective tissue which is a major component of bone, skin, muscles, tendons, and cartilage.

The organic component of bone also includes at least two vitamin K‐dependent Gla proteins; osteocalcin and matrix Gla protein (MGP) (Azuma et al, 2014; Zhou et al, 2021). These proteins need vitamin K as a cofactor to allow them to bind to calcium ions in the bone matrix (Shearer et al, 2012).

Bone also functions as an important mineral reserve. 70% of the mineral component is hydroxyapatite composed primarily of calcium and phosphate, magnesium, and other minerals in lesser amounts (Bronner, 2001; Boskey, 2013; Murshed, 2017; Whyte, 2017).

The collagen proteins give bones their flexibility, and the hydroxyapatite gives them strength and rigidity. These components together, allow bone to act as a scaffold for muscle and other organs, protecting the organs from injury while forming a load-bearing framework that allows physical activity to take place (Russo, 2009). It is this combination that gives us ‘good bone’.

Bone Building
Important bone building occurs during childhood, through adolescence and early adulthood, up to the mid-20s. For most people, bone mass peaks around the age of 35. At around age 40, bone density begins to decrease. In women, the speed of bone loss accelerates with the onset of menopause. If adequate bone was not built during childhood, a person is at risk for weaker bones in adulthood (Weaver et al, 2016).

Physical activity and appropriate nutrition are required for your skeleton to achieve its peak bone mass, density, and flexibility. An important aspect of bone building in childhood is physical activity, playing outside, and engaging your body in movement (Robling & Turner, 2009; Arfat et al, 2014; Klein-Nulend et al, 2013).

Research supports the importance of activity to build bone during childhood. Studies of amateur male soccer players (age 19-27 years) with a long training history have increased bone mineral content and bone mineral density at the lumbar spine (13% and 10% respectively), femoral neck (24% and 21%) and lower limbs (16% and 10%), compared to age, height, and weight-matched sedentary males from the same Caucasian population (Calbet et al, 2001).

Research shows that female adolescent athletes achieve better peak bone mass, especially if they start before puberty (Bass, Saxon et al, 2002; Seaman, 2002; Vincent-Rodriguez et al, 2004). Gymnastics generates strong ground reaction forces on the body. Research on 9-year- old girls in gymnastics, report that they have a 5.7% higher bone mineral density in their upper extremities compared to sedentary subjects (Vincent-Rodriguez et al, 2007).

Diet and nutrition are also critical for bone building in childhood. As an example, rickets is the softening and weakening of bones in children, because of prolonged vitamin D deficiency. Vitamin D helps your body absorb calcium and phosphorus from food. If vitamin D is low, then the absorption is insufficient and there is not enough of these nutrients to build healthy bones. This causes a mineralization defect in the skeleton that results in growth retardation and many of the skeletal manifestations seen in vitamin D deficiency (David, 1991; Pettifor, 2005; Thatcher et al, 1999). The fortification of milk with vitamin D resulted in almost complete eradication of the disease (Holick, 2006).

A current example would be the popularity of drinking large amounts of carbonated beverages. Many soft drinks or colas contain a high content of phosphoric acid (phosphate) which is used to enhance flavor. The phosphoric acid interferes with calcium and magnesium absorption and results in a loss of calcium from bone. Drinking large amounts of these beverages during childhood can reduce the mineral density in bones (Tucker et al, 2006; Ahn & Park, 2021).

Bone Maintenance
Bone remodeling occurs after the skeleton has reached maturity during adulthood, and is necessary to maintain the structural integrity of bone, its mass, and the calcium and phosphate homeostasis that has been achieved during childhood (Feng & McDonald, 2011; Wein & Kronenberg, 2018). Remodeling repairs the bone by removing old and micro-damaged bone, replacing it with strong new bone.

Bone remodeling is regulated by osteoblasts—cells that build up the skeleton—and osteoclasts—cells that break down the skeleton. Osteoblasts, which are a form of immature bone cells, help produce a matrix composed of collagen that becomes mineralized and forms bone (Manolagas, 2000). Osteoclasts work to get rid of old, weakened bone. They resorb old bone to make room for the creation of strong healthy bone. Continuous new bone matrix synthesis is followed by calcification of the newly formed bone (Mera et al, 2018). If the bone-forming activity (ie, absorption) is greater than the breakdown of bone (ie, resorption), the process of maintaining a healthy bone structure is maintained. Through remodeling, the entire skeleton is replaced every 7 to 10 years.

Role of Exercise on Bone
Bone is a dynamic tissue that interacts with and responds to physical activity and exercise. Physical activity creates load and forces on bones through the contractile activity of muscles and through ground reaction forces (Rubin et al, 2023; Vu Nguyen et al, 2018; LeBlanc et al, 2021). (Ground reaction forces are exerted by the ground on the body as contact is made, and the force accelerates with movement -also referred to as mechanotransduction.) When your muscles pull on your bones, it responds during the moment, while also starting a cascade of biochemical signals that will begin to strengthen those areas of the bone (Goodman et al, 2015). The harder the muscles tug, the more your body renews and strengthens those bones through increased calcium deposits; accordingly, bones become denser and stronger.

These physical forces result in maintaining or gaining of bone mass and drive the adaptation of bone structure. Bone traits, such as density, strength, and architecture, respond and adapt to help the skeleton to cope with the loading environment while preventing injuries (Sharkey et al, 1995, Lu et al, 1997; Burr, 1997).

Stresses that cause osteogenesis, or bone building, must be variable, dynamic, and progressive; static loading does not cause osteogenesis (Lanyon, 1984; Burr et al, 2002). Impact or gravitational forces (ie, running, walking, stair climbing) and non-impact or muscle forces (ie, weight-lifting, swimming) are both important for skeletal regulation.

Forty-three healthy adults engaged in six months of supervised exercise training were studied. They found that a combination of aerobic, resistance, and flexibility exercises done on average 2.5 hours per week reduced markers of bone resorption and increased the production of markers of bone building (Smith et al, 2016). Participants divided their time between aerobic exercises (57%), resistance exercises (35%), and flexibility exercises (8%) and spent an average of 71 minutes in each training session.

Cross-sectional studies involving adult subjects and using bone mineral density measurements have shown that exercises involving high impact (e.g., jumping) and high resistance (e.g., weightlifting) appear to be particularly effective in improving bone mass and content, especially when the intensity of the exercise is high, and the speed of movement is elevated. Loaded (weight-bearing) aerobic exercises such as walking or running also have the potential to improve bone mass in adults and have the added benefit of improving cardiovascular conditioning (Maimoun & Sultan, 2011; Guadalupe-Grau et al, 2012; Janik et al, 2018).

Role of Nutrition in Bone
While exercise is important to maintain bone health, it is also important to continue adequate nutrition. As appropriate nutrition in childhood helps your bones achieve peak mass, it is important to maintain appropriate nutrition, as you age, to ensure that your bones receive nutrients key to their health.

Some of these nutrients include vitamin K, vitamin D, and astaxanthin. Below we will review the research on how each of these nutrients help your bone. There is not research on athletes and their bone health, specifically, other than regarding stress fractures. However there is much research on bone health amongst older adults, so we are referencing that research as we believe it is very applicable.

Vitamin K and Bone
Vitamin K is not a single entity but, rather, a family of structurally related molecules derived from different sources. There is vitamin K1, aka phylloquinone which can be found in green leafy vegetables. Vitamin K2, aka menaquinone, can be found in natto, sauerkraut, hard cheeses, beef, pork, egg yolks, and chicken, etc, with some produced by gut bacteria.

There are many proteins in bone that depend on vitamin K to be active. These proteins include osteocalcin (OC), matrix Gla protein (MGP), gas 6, periostin, and protein S (Fusaro, et al, 2017). When vitamin K is part of your diet, it activates these proteins and improves your bone health.

There is a wealth of research on the importance of vitamin K and bone health, and how K supports physical activity and fitness. Physical movement and exercise require your bones to be strong and solid, so they can power movement, and not suffer fractures of any kind. Bone diseases such as osteopenia, osteoporosis and arthritis impact bone function and interfere with exercise. The research shows that vitamin K helps to preserve bone health in multiple ways.

Osteocalcin
Osteoblast cells in bone produce the protein osteocalcin, which is the most abundant protein found in the bone matrix. However, the newly made osteocalcin is inactive and it needs vitamin K to become fully activated so it can bind calcium. That requirement alone makes vitamin K a major player in bone health, and subsequently a major player for optimal fitness and physical activity (Hauschka, 1986; Ferron et al, 2010). cOC is the term used for osteocalcin that has been carboxylated and activated.

When there is sufficient vitamin K, osteocalcin is able to take calcium from the blood circulation and bind it to the hydroxyapatite in the bone matrix, enabling mineralization and making the skeleton stronger (Huschka, 1986; Neve, 2013).

Total circulating levels of the bone protein osteocalcin (OC) have been shown to be a sensitive marker of bone formation and bone turnover, and is considered a BTM, Bone Turnover Marker. The degree of osteocalcin carboxylation is responsive to vitamin K intake, and is also used as a relative indicator of vitamin K status as well (Gundberg et al, 2012). In a study of healthy girls, plasma phylloquinone was inversely correlated with circulating cOC concentrations showing that a better vitamin K status was associated with decreased bone turnover in healthy girls (Kalkwarf et al, 2004).

Exercise is sensed by bone cells. The mechanical stress on the skeleton initiates strains that are recognized by bone cells, and they start a cascade of events that lead to stronger bone. Their response can be measured by bone turnover markers (BTM), such as osteocalcin, which increase during exercise. Multiple clinical studies show that osteocalcin levels increase during exercise in different gender and age groups (Adami et al, 2008; Banfi et al, 2010; Jürimäe et al, 2011; Vasikaran et al, 2011; Lin et al, 2012; Brotto & Johnson, 2014; Levinger et al, 2016; Hiam et al, 2019; Rahimi et al, 2020; Chowdhury et al, 2020; Smith et al, 2021; Rahimi et al, 2021).

For example, after six months of regular activity consisting of a combination of aerobics (60%), resistance exercise (weightlifting) (30%), and flexibility-enhancing exercise (stretching) (10%), trained subjects had a 9.8% increase in OC and a 16% decrease in CTx (Smith et al, 2016). And upon discontinuation of training, there was a significant decrease in osteocalcin (Koundourakis et al, 2019; Weiler et al, 2012)

Bone Formation
Research shows that a high intake of MK4 daily (45 mg) activated osteocalcin, and bone density increased, indicating a correlation between K2 and bone health (Ozuru et al, 2002). Lab studies showed increased osteocalcin production after exposure of osteoblasts to Vitamin K2 (Matsunaga et al, 1999; Koshihara et al, 2003) and increased expression of genes that form bone (Akbari & Rasouli‐Ghahroud, 2018).

Bone Density
Studies of people around the world have shown that vitamin K improves the markers of bone building and bone mineral density (BMD). A Korean study showed that administering 15 mg of vitamin K2 (MK4) three times daily, for six months to postmenopausal women significantly increased the bone density of the lumbar spine while increasing the level of cOC (Shiraki et al, 2000; Je et al, 2011). Taking 1.5 milligrams of MK4 daily increased the serum levels of cOC in postmenopausal Norwegian women compared to a group who received a placebo (Emaus et al, 2010). Another study showed that subjects given 200 micrograms of MK7 had an increase in cOC, indicating better bone quality for postmenopausal women, while those who were not given MK7 had an increase in ucOC (reflecting a deficiency of vitamin K) (Inaba et al, 2015). Post-menopausal Japanese women with osteoporosis taking MK4 for 6-12 months showed significant improvement of vertebral BMD (Koitaya et al, 2014). Postmenopausal Syrian women, without estrogen replacement therapy, had a positive correlation of their K1 levels with lumbar spine bone mineral density, indicating that measures of K1 might be a valuable diagnostic tool (Jaghsi et al, 2018).

A study in the Netherlands of postmenopausal women showed that taking 45 mg/day of MK4 for three years prevented loss of hip bone strength, whereas the group who did not receive MK4 had a significant loss of bone (Knapen et al, 2007).

Osteoporosis is correlated with increased bone turnover without equivalent bone building. The deficiencies of calcium and phosphorus in osteoporotic women increase bone resorption, which frees osteocalcin to circulate in the blood. This may explain the increased concentrations of osteocalcin in the blood levels of osteoporotic post-menopausal women and the data showing that ucOC levels were negatively correlated with bone mineral density (Kalaiselvik et al, 2013; Susanto, 2011; Hendrijantini et al, 2016).

Huang (et al, 2015) performed a meta-analysis of 19 clinical trials, which included 6759 participants. The data supported the role of vitamin K2 in the maintenance and improvement of vertebral bone mineral density and the prevention of fractures in postmenopausal women with osteoporosis.

Another review involving a total of 6,425 subjects found a significant improvement in lumbar spine bone mineral density when given vitamin K2, and a significant reduction in fracture incidence (Akbari et al, 2018).

Bone Strength
Bone matrix is a dynamic, two-part system in which the mineral part provides the stiffness, and the collagen-fibers part provides flexibility allowing the bone to absorb energy from a fall and not break. Collagen occupies more than half the volume of bone and makes the foundations on which calcium and other minerals accumulate. Collagen accumulation is critically important for high quality bone formation. Therefore, destruction of bone collagen can increase fracture risk.

In addition to OC carboxylation, which modulates the deposition of calcium in bone, MK-4 has been shown to increase collagen accumulation (Ichikawa et al, 2006). Also, MK-7 increased collagen production through osteoblastic cells (Sato, 2012).

Reduces Risk of Fractures
Exercise and physical activity require weight and load to be placed on bones. Research shows that both vitamin K1 and K2 reduce the risk of fractures and microfractures.

Low dietary vitamin K consumption and a high proportion of ucOC are independent risk factors for bone fractures in mature populations (Szulc et al, 1993; Seibel et al, 1997; Vergnaud et al, 1997; Fusaro et al, 2020; Shiraki et al, 2000 ; Bolton-Smith et al, 2007; Tsugawa et al, 2008; Binkley et al 2009; Rønn et al, 2016).

Large-scale epidemiological studies on the relationship between vitamin K and fracture risk have been conducted. One of the largest studies in this matter is a prospective analysis conducted within the Nurse' Health Study performed with 72,327 women between 38 and 74 years of age, who were followed for ten years. In that study, subjects with a vitamin K1 intake more than 109 μg/day presented a 30% lower risk of hip fracture than women with a lower intake of vitamin K (Feskanich et al, 1999; Booth et al, 2000).

MK4 has been shown to decrease fractures and has been approved by the Ministry of Health in Japan since 1995 for the treatment of osteoporosis and osteoporosis pain. Multiple clinical trials using 45 mg per day of MK4 show that this amount taken daily may decrease fractures more than 80% independent of the number of falls sustained (Ishida, 2008).

A clinical trial evaluated the efficacy of 45 mg daily MK4 for reducing fracture risk and improving bone mineral density over a two-year period. They enrolled 241 osteoporotic women (average age 67 years). The control group (n = 121) received 150 mg elemental calcium per day, while the treatment group (n = 120) consumed 150 mg elemental calcium plus 45 mg MK4 daily. After 24 months of treatment, the control group sustained 30 vertebral fractures for a fracture rate of 30.3%, while the treatment group sustained 13 vertebral fractures for a fracture rate of 10.9%. The decrease in fractures in the MK4 group was highly statistically significant (p = 0.0273). Similarly, the control group exhibited two fractures in the femoral neck, compared to no femur fractures in the treatment group. (Shiraki et al, 2000).

Another clinical trial evaluated 45 mg of MK4 daily, along with 1000 IU of vitamin D2 and 600 mg calcium in ambulatory women with Alzheimers. The control group were healthy, active, elderly women living independently in the community who received no intervention. After two years, the control group suffered 22 fractures while there were only 3 fractures in the treatment group. Overall, there were 86% fewer nonvertebral fractures (p = 0.0003) in the treatment group compared to controls and 87% fewer hip fractures (p = 0.0022) in the treatment group compared to controls (Sato et al, 2004).

Tip: Since the time of these trials, calcium intake has been found to have serious side effects, and is no longer recommended as a stand-alone supplement.

A meta-analysis evaluated clinical trials on MK4 and fracture risk. They identified 13 randomized, controlled trials of the effect of MK4 on osteoporosis. Of those, seven had fracture risk as an end point and thus were included in their meta-analysis. From these studies, they concluded that intake of 45 mg of MK4 a day decreases vertebral fracture by 60%, hip fracture by 73%, and all nonvertebral fractures by 81% (Cockayne et al, 2006).

MK4 also has been cited as a potential strategy for drug-induced bone loss, such as osteoporosis caused by prednisone. In clinical trials, MK4 (45 mg daily) prevented bone loss and/or fractures caused by deficiency (Ishida, 2008).

Healthy postmenopausal women who took MK7 for three years, showed less bone loss in the lumbar spine and femoral neck, than those who did not take MK7. They also showed greater bone strength (Knapen et al, 2013).

A meta-analysis (Huang et al, 2015) looked at the role of vitamin K2 supplements both in BMD and fracture. Including 19 studies with 6759 participants, the authors found that K2 supplements improved significantly middle- and long-term vertebral BMD and long-term forearm BMD in postmenopausal women with osteoporosis, and reduced fracture risk in women with osteoporosis.

Low plasma concentrations of vitamin K are associated with a high risk of bone fractures in both northern European and Asian populations of both sexes (Yaegashi et al, 2008; Torbergsen et al, 2015). The NOREPOS study (Norwegian Epidemiologic Osteoporosis Study) showed that low serum levels of vitamin K1 were associated with a 50% higher risk for hip fractures (Finnes et al, 2016). Another study showed that a low concentration of vitamin K1 in elderly Asian patients was associated with an increased risk of fractures in both sexes (Nakano et al, 2011).

A pilot study indicated that children with low vitamin K2 status may be at greater risk of developing low-energy bone fractures. A low-energy bone fracture is defined as a fracture resulting from a fall that happens from standing height or lower (Popko et al, 2018; Karpinski et al, 2017).

Stress fractures occur due to repetitive loading of the bones with stress, rather than a single traumatic event. They can occur in all bones of the lower extremity, particularly in people predisposed to repetitive strain, such as athletes. A recent report was published of a 13-year-old basketball player with right foot pain. After six weeks of standard treatment, his pain had increased. When testing showed he was low in vitamin K levels, he was told to add green vegetables to his diet. He returned to the sport in six months and his physician felt that correcting the vitamin K deficiency was an important factor (Bayramoğlu et al, 2017). A closer look at the role of vitamin K and stress fractures can be found at this link- Stress Fractures

A recent meta-analysis involving a total of 80,982 participants, showed an inverse association between dietary vitamin K1 intake and the risk of fractures. Those subjects with the highest intake of vitamin K presented a 22% reduction in fracture risk (Hao et al, 2017). The prevalence of VK deficiency was found to be higher in older patients (mean age 80.0) with hip fractures than those without (Bultynck et al, 2020).

Japanese Shorinji Kempo athletes were given a medical exam showing that 44% of them had experienced a sports-related fracture during practice, 75% had a lower daily vitamin D intake, and 94% had a lower daily vitamin K intake. The authors indicated that the athletes needed to improve their bone mass, bone metabolism, and improve their nutrition, including vitamin K in order to improve their physical function (Sumida et al, 2012). Improving the intake of vitamin K with an increased intake of green leafy vegetables substantially improved osteocalcin markers of bone health suggesting increased entry of osteocalcin into the bone matrix, improvement of bone quality and lower fracture risk (Sim, et al, 2020).

In Australia, women with the lowest intake of vitamin K1 had the highest long-term risk for fractures. Women were followed over 14.5 years and their intake of vitamin K was measured via osteocalcin blood levels. The Perth Longitudinal study of aging Women in Australia showed that women who ate 125 g of dark leafy vegetables or more than 100 micrograms of vitamin K1, were 31% less likely to have any fractures (Sim et al, 2020). Lead author Dr. Marc Sim said the results further solidified vitamin K1 as a factor in fracture risk. Higher Vitamin K1 is associated with lower long-term risk for any fracture- and hip fracture-related hospitalization in community- dwelling older women (Sim, et al 2022).

These findings apply to postmenopausal women as well. A four-year study was conducted with postmenopausal Canadian women with osteopenia and normal levels of vitamin D who were taking vitamin K1 (phylloquinone) 500 mcg/day. The women taking vitamin K had fewer clinical fractures than the placebo group of women (Cheung et al, 2008). Recently, postmenopausal women with osteoporosis were studied, and the results showed that those with fractures had a significantly lower value of vitamin K1 (Yaegashi et al, 2008; Torbergsen et al, 2015; Moore et al, 2020).

Vitamin D and Bone
Vitamin D is also important for bone health. Vitamin D is a fat-soluble vitamin that is naturally synthesized by the skin following exposure to the ultraviolet rays of the sun. Vitamin D plays a main role in regulating calcium metabolism by increasing intestinal calcium absorption from the food you eat (Bouillon, 2001; Holick, 2006; Fleet, 2017). When you don’t consume enough calcium, vitamin D maintains its blood levels by drawing on the body’s main calcium supply — your bones (Eisman & Bouillon, 2014).

Bone Formation
It is documented that vitamin D stimulates bone formation and increases the level of parathyroid hormone (PTH), which stimulates the activity of osteoclasts in the bone, removing old bone and improving bone quality (Goolsby & Boniquit, 2017; Saliba et al, 2011).

Bone Mass
Foo et al. (2009) examined the relationship between 25(OH)D status and bone mass, bone turnover, and muscle strength in Chinese adolescent females (n = 301) and found that poor vitamin D status (blood levels <20 ng/mL) was associated with reduced forearm strength, (using a handgrip dynanomometer) when compared to individuals with adequate vitamin D levels (>20 ng/mL).

25(OH)D deficiency was associated with lower serum uncarboxylated osteocalcin and lower bone mineral content in Danish girls, although a vitamin D supplement of 400 IU/day for 12 months did not increase serum osteocalcin (O’Connor et al. 2007)

A study examining male Finnish military recruits found vitamin D status to be a significant determinant of maximal peak bone mass and also discovered that 25(OH)D levels below 30 ng/mL significantly increased the risk of stress fractures in this subject group (Valimaki et al, 2004).

Bone Remodeling
Bone remodeling is necessary to maintain the bone health. The osteoclast cells in bone resorb the old bone to make room for the creation of strong, healthy bone, which is produced by osteoblasts. Without this cycle of bone remodeling, new healthy bone is not formed. Anything that interferes with resorption leaves a bone full of fragile, old cells that can fracture easily.

One study looked at the effect of intense physical activities on bone metabolism, bone mineral density and bone biochemical markers in male decathletes, mean age 22.4 years, in training. They found that bone density was higher in athletes, they had higher concentrations of osteocalcin (59.8%), higher concentrations of type-1 collagen (41.4%) and vitamin D3 (37.1%), and high bone turnover (Maimoun et al, 2008).

Another study evaluated the blood levels of vitamin D3, the parathyroid hormone, and bone turnover markers including osteocalcin, as well as the intake of calcium and vitamin D from their diet of football (soccer) players in Poland. They found that the levels of D3 were significantly higher in the group of active football players (80.09%), when compared to inactive controls, which indicates a positive impact of intensive physical exercise on bone formation (Solarz et al, 2014).

Supplementing with vitamins D and K has been shown to induce osteocalcin and bone building (Gigante et al, 2015).

A recent study looked at young athletes in football (soccer) training, who were given vitamin D3 in a dose of 20,000 IUs twice a week for eight weeks, compared to a group undergoing the same training but without the vitamin D3. They found that osteocalcin levels increased by 9% and markers of resorption increased by 14% in those who received the D3, a positive reflection of the bone formation and remodeling process (Brzezianski et al, 2022).

Fracture Reduction
The literature on bone fractures and vitamin D among the general population is mixed.

People over 65, living independently, received vitamin D injections of 100,000 IU of oral vitamin D3, on a quarterly basis over five years. 2037 were men and 649 were women. The total fracture rate was reduced by 22% and fractures in major sites (hip, wrist, forearm or vertebrae) were reduced by 33% (Trivedi et al, 2003).

A meta-analysis showed that low serum 25(OH)D level is associated with a higher risk of hip fracture in older people (Ghahfarrokhi et al, 2022)

A review of the National Database in Japan showed that those patients with osteoporosis who were prescribed vitamin D had a significantly lower rate of new fractures, dropping by almost 50% when compared to patients who did not take vitamin D (Yakabe et al, 2023). Though, a trial from Australia showed no reduction in fractures for adults age 60-84 years who took 60,000 IUs a month for up to five years, though the longer you took the D3, the more the risk of fractures declined (Waterhouse et al, 2023). This trial did not measure vitamin D levels throughout the study or whether the subjects were on any medications.

However, there is a great deal of research on stress fractures, which are defined as a micro-break or crack in the bone. While a regular fracture is a traumatic injury that occurs immediately during impact, a stress fracture develops over time, typically due to abnormal and repetitive loading from exercise. More on the topic of stress fractures can be found at this page.

Vitamin D and Osteocalcin
Vitamin D was also found to stimulate production of vitamin K-dependent proteins, like osteocalcin (Owen et al, 1991; Bunyaratavej, 2015; Kato et al, 2015). Previous basic studies showed that the rate of osteolcalcin and MGP secretion increased after treatment with vitamin D (Fraser et al, 1988), meaning that increased intake of vitamin D can help build bone.

Summary
Bones are a dynamic tissue that undergo continuous growth and remodeling. The cycle of bone requires both physical activity as well as nutrition which contain the elements that build healthy bone. The research indicates that vitamin K is a major factor in bone health, as it activates important proteins involved in bone building. These proteins help bind calcium to the bone matrix. Vitamin K reduces the risk of bone fractures, it builds healthy bones, and it increases bone density and strength. Vitamin D has an important role as it regulates calcium absorption from your diet. Vitamin D has also been found to correlate with other markers of bone health.

References

Adami, S, et al., Physical activity and bone turnover markers: a cross-sectional and a 417 longitudinal study. Calcified Tissue International. 2008;83(6):388-392.

Ahn H, Park YK. Sugar-sweetened beverage consumption and bone health: a systematic review and meta-analysis. Nutr J. 2021 May 5;20(1):41.

Akbari S, Rasouli-Ghahroudi AA. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. Biomed Res Int. 2018;2018:4629383.

Arfat Y, Xiao W-Z, Iftikhar S, Zhao F, Li D-J, Sun Y-L, et al. Physiological effects of microgravity on bone cells. Calc Tissue Int. 2014;94:569-579.

Akbari S, Rasouli-Ghahroudi AA. Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies. Biomed Res Int. 2018;2018:4629383.

Azuma K, Ouchi Y, Inoue S. Vitamin K: novel molecular mechanisms of action and its role in osteoporosis. Geriatr Gerontol Int. 2014 Jan;14(1):1-7.

Banfi G, Lombardi G, Colombini A, Lippi G. Bone metabolism markers in sports medicine. Sports Med. 2010 Aug 1;40(8):697-714.

Bass SL, Saxon L, Daly RM, Turner CH, Robling AG, Seeman E. The effect of mechanical loading on the size and shape of bone in pre-, peri-, and postpubertal girls: a study in tennis players. J Bone Miner Res. 2002 Dec;17(12):2274-80.

Bayramoğlu M, Ünlütürk, N. Nonhealing, progressive stress fractures of the foot in a 13-year-old basketball player: is vitamin K deficiency a risk factor? J Phys Ther Sci. 2017 Apr;29(4):763-766.

Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, et al. Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Min Res. 2009;24:983–991.

Bolton-Smith C, McMurdo MET, Paterson CR, Mole PA, Harvey JM, Fenton ST, et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res. 2007 Apr; 22(4):509-19.

Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr. 2000;71:1201–1208.

Bultynck C, Munim N, Harrington D, Judd, L, Ataklte F, Shah Z, et al. Prevalence of vitamin K deficiency in older people with hip fracture. Acta Clin Belg. 2020;75:136–140.

Bunyaratavej J. The intriguing correlation between undercarboxylated osteocalcin and vitamin D. J Med Assoc Thai. 2015;98(Suppl 8):S16-S20.

Burr DB. Muscle strength, bone mass, and age-related bone loss. JBMR. 1997 Oct;12(10):1547-1551.

Boskey AL. Bone composition: relationship to bone fragility and antiosteoporotic drug effects. Bonekey Rep. 2013;2:447.

Bouillon R. Vitamin D: from photosynthesis, metabolism, and action to clinical applications. In: De Groot L, Jameson JL, Burger HG, editors. Endocrinology. 3^rd ed. Philadelphia, USA: Saunders; 2001. p. 1009–1028.

Bronner, F. Extracellular and intracellular regulation of calcium homeostasis. Sci World J. 2001;1:919–925.

Brotto M, Johnson ML. Endocrine crosstalk between muscle and bone. Curr Osteoporos Rep. 2014;12:135-141.

Brzeziański M, Migdalska-Sęk M, Czechowska A, Radzimiński Ł, Jastrzębski Z, Brzeziańska-Lasota E, et al. Correlation between the positive effect of vitamin D supplementation and physical performance in young male soccer players. Int J Environ Res Public Health. 2022 Apr 23;19(9):5138.

Calbet JA, Dorado C, Diaz-Herrera P, Rodriguez-Rodriguez LP. High femoral bone mineral content and density in male football (soccer) players. Med Sci Sports Exerc. 2001 Oct;33(10):1682-7.

Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): A randomized controlled trial. PLoS Med. 2008;5:e196.

Chowdhury, S., et al., Muscle-derived interleukin 6 increases exercise capacity by signaling in 425 osteoblasts. J Clin Invest, 2020;130(6):2888-2902.

Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ. Vitamin K and the Prevention of Fractures. Arch Int Med. 2006;166:1256–1261.

David L. Common vitamin D₃ deficiency rickets. In: Gloreaux FH, editor. Rickets. Nestle nutrition workshop series. New York, New York, USA; Raven Press; 1991. p.107–122.

Eisman JA, Bouillon R. Vitamin D: Direct effects of vitamin D metabolites on bone: lessons from genetically modified mice. Bonekey Rep. 2014 Feb 5;3:499.

Emaus N, Gjesdal CG, Almås B, Christensen M, Grimsgaard A, Berntsen G, et al. Vitamin K2 supplementation does not influence bone loss in early menopausal women: A randomised double-blind placebo-controlled trial. Osteoporos Int. 2010;21:1731–1740.

Feng X, McDonald JM. Disorders of Bone Remodeling. Annual Review of Pathology. 2011;6:121-145.

Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePiknho RA, Teti A, Ducy P, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010 Jul 23;142(2):296-308.

Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA. Vitamin K intake and hip fractures. in women: A prospective study. Am J Clin Nutr. 1999;69:74–79.

Finnes TE, Lofthus CM, Meyer HE, Søgaard AJ, Tell, GS, Apalset EM, et al. A combination of low serum concentrations of vitamins PK and D is associated with increased risk of hip fractures in elderly Norwegians: A NOREPOS study. Osteoporos Int. 2016;27:1645–1652.

Fleet JC. The role of vitamin D in the endocrinology controlling calcium homeostasis. Molecular and Cellular Endocrinology. 2017;17:30221–30226.

Foo LH, Zhang Q, Zhu K, Ma G, Hu X, Greenfield H, et al. Low vitamin D status has an adverse influence on bone mass, bone turnover, and muscle strength in Chinese adolescent girls. J Nutr. 2009 May;139(5):1002-1007.

Fraser JD, Price PA. Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. J Biol Chem. 1988 Aug 15;263(23):11033–11036.

Fusaro M, Mereu MC, Aghi A, Iervasi G, Gallieni M. Vitamin K and bone. Clin Cases Miner Bone Metab. 2017 May-Aug;14(2):200-206.

Fusaro M, Cianciolo, G, Brandi ML, Ferrari S, Nickolas TL, Tripepi G, Plebani, et al. Vitamin K and Osteoporosis. Nutrients. 2020;12:3625.

Ghahfarrokhi SH, Mohammadian-Hafshejani A, Sherwin CMT, Heidari-Soureshjani S. Relationship between serum vitamin D and hip fracture in the elderly: A systematic review and meta-analysis. J Bone Miner Metab. 2022 doi: 10.1007/s00774-022-01333-7.

Gigante A, Bruge F, Cecconi, S, Manzotti S, Littarru GP, Tiano L. Vitamin MK-7 enhances vitamin D3-induced osteogenesis in hMSCs: Modulation of key effectors in mineralization and vascularization. J. Tissue Eng Regen Med. 2015;9:691–701.

Goolsby MA, Boniquit N. Bone health in athletes. Sports Health. 2017 Mar-Apr;9(2):108-117.

Goodman CA, Hornberger TA, Robling AG. Bone and skeletal muscle: key players in mechanotransduction and potential overlapping mechanisms. Bone. 2015;80:24–36.

Guadalupe-Grau A, Fuentes T, Guerra B, Calbet JAL. Exercise and bone mass in adults. Sports Med. 2012 Nov 25;39:439-468.

Gundberg CM, Lian JB, Booth SL. Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr. 2012;3(2):149-157.

Hao G, Zhang B, Gu M, et al. Vitamin K intake and the risk of fractures: a meta-analysis. Medicine (Baltimore). 2017;96(17);e6725.

Hauschka PV. Osteocalcin: the vitamin K-dependent Ca2+-binding protein of bone matrix. Haemostasis. 1986;16(3–4):258–272.

Hendrijantini N, Alie R, Setiawati R, Astuti ER, Wardhana MP. The correlation of bone mineral density (BMD), body mass index (BMI) and osteocalcin in postmenopausal women. 2016;8:6–10. doi: 10.4172/0974-8369.1000319

Hiam D, Voisin S, Yan, XU, Landen S, Jacques M, Papadimitriou ID, et al. The association between bone mineral density gene variants and osteocalcin at baseline, and in response to exercise: The gene SMART study. Bone. 2019 Jun;123:23-27.

Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clinic Proc. 2006 Mar;81(3):353-73.

Huang Z-B, Wan S-L, Lu Y-J, Ning L, Liu C, Fan S-W. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2015 Mar;26(3):1175-1186.

Inaba N, Sato T, Yamashita T. Low-dose daily intake of vitamin K(2) (Menaquinone-7) improves osteocalcin γ-carboxylation: a double-blind, randomized controlled trials. J Nutr Sci Vitaminol. 2015;61(6):471-80.

Ishida Y. Vitamin K2. Clin Calcium. 2008 Oct;18(10):1476-82.

Jaghsi S, Hammoud T, Haddad S. Relation between circulating vitamin K1 and osteoporosis in the lumbar spine in Syrian post-menopausal women. The Open Rheumatology Journal. 2018;12(1):1–9.

Janik M, Stuss M, Michalska-Kasiczak M, Jegier A, Sewerynek E. Effects of physical activity on sclerostin concentrations. Endokrynol Pol. 2018;69(2):142–149.

Je SH, Joo N.-S, Choi B.-H, Kim K-M, Kim B-T, Park S.-B, et al. Vitamin K supplement along with vitamin D and calcium reduced serum concentration of undercarboxylated osteocalcin while increasing bone mineral density in Korean postmenopausal women over sixty-years-old. J Korean Med Sci. 2011;26:1093–1098.

Jürimäe J, Rämson R, Mäestu J, Jürimäe T, Arciero PJ, Braun WA, et al. Interactions between adipose, bone, and muscle tissue markers during acute negative energy balance in male rowers. J Sports Med Phys Fitness. 2011;51:347–54.

Ichikawa T, Horie-Inoue K, Ikeda K, Blumberg B, Inoue S. Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem. 2006;281:16927–16934.

Kalaiselvi VS, Prabhu K, Ramesh M, Venkatesan V. The association of serum osteocalcin with the bone mineral density in post menopausal women. J Clin Diagnostic Res. 2013;7:814–6. doi: 10.7860/JCDR/2013/5370.2946

Kalkwarf HJ, Khoury JC, Bean J, Elliot JG. Vitamin K, bone turnover, and bone mass in girls. Am J Clin Nutr. 2004;80:1075–80.

Karpinski M, Popko J, Maresz K, Badmaev V, Stohs SJ. Roles of vitamins D and K, nutrition, and lifestyle in low-energy bone fractures in children and young adults. J of Am College of Nutrition. 2017;36(4):399-412.

Kato H, Ochiai-Shino H, Onodera S, Saito A, Shibahara T, Azuma T. Promoting effect of 1,25(OH)2 Vitamin D3 in osteogenic differentiation from induced pluripotent stem cells to osteocyte-like cells. Open Biol. 2015 Feb;5(2):140201.

Klein-Nulend J, Bakker AD, Bacabac RG, Vatsa A, Weinbaum S. Mechanosensation and transduction in osteocytes. Bone. 2013 Jun;54(2):182-90.

Knapen M, Schurgers, Vermeer C. Vitamin K 2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007;18:963–972.

Knapen M, Drummen N, Smit E, Vermeer, C, Theuwissen E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int. 2013;24:2499–2507.

Koitaya N, Sekiguchi M, Tousen Y, Nishide Y, Morita A, Yamauchi J, et al. Low-dose vitamin K2 (MK4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J Bone Miner Metab. 2014 Mar;32(2):152-50.

Koshihara Y, Hoshi K, Okawara R, Ishibashi H, & Yamamoto S. Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture. Journal of Endocrinology. 2003;176(3):339–348.

Koundourakis NE, Androulakis N, Dermitzaki E, Venihaki M, Margioris AN. Effect of a 6-week supervised detraining period on bone metabolism markers and their association with ergometrics and components of the hypothalamic-pituitary-gonadal (HPG) axis in professional male soccer players. J Bone Miner Metab. 2019;37(3):512–519.

Lanyon LE, Rubin CT. Static vs dynamic loads as an influence on bone remodeling. J Biomechanics. 1984;17(2):897-905.

LeBlanc M, Burdullis A, McKinnon M, Hawkins S. Relationships between vertical ground reaction force values and bone mineral density values in male runners. Med & Sci in Sports & Exer. 2021 Aug;53(8S):113.

Levinger I, Lin X, Zhang X, Brennan-Esperanza TC, Volpato B, Hayes A, et al. The effects of muscle contraction and recombinant osteocalcin on insulin sensitivity ex vivo. Osteoporos Int. 2016 Feb;27(2):653-63.

Lin C-F, Huang T-H, Tu K-C, Lin LL, Tu Y-H, Yang R-S. Acute effects of plyometric jumping and intermittent running on serum bone markers in young males. Eur J Apply Physiol. 2012 Apr;112(4):1475-84.

Lu T-W, Taylor SJG, O’Connor JJ, Walker PS. Influence of muscle activity on the forces in the femur: an in vivo study. J Biomech. 1997 Nov-Dec;30(11-12):110-1106.

Maïmoun L, Coste O, Puech AM, Peruchon E, Jaussent A, Paris F, et al. No negative impact of reduced leptin secretion on bone metabolism in male decathletes. Eur J Appl Physiol. 2008;102(3):343–351.

Maïmoun L, Sultan C. Effects of physical activity on bone remodeling. Metabolism. 2011;60(3):373–388.

Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21:115–37.

Matsunaga T, Inoue H, Kojo T, Hatano K, Tsujisawa T, Uchiyama C, et al. Increase in the potential of osteoblasts to support bone resorption by osteoclasts in vitro in response to roughness of bone surface. Calc Tissue Int. 2014 Jan 31;65:454-58.

Mera P, Ferron M, Mosialou J. Regulation of energy metabolism by bone-derived Hormones. Cold Spring Harb Perspect Med. 2018 Jun;8(6):a031666.

Moore AE, Kim E, Dulnoan, D, Dolan AL, Voong, K, Ahmad I, et al. Serum vitamin K 1 (phylloquinone) is associated with fracture risk and hip strength in post-menopausal osteoporosis: A cross-sectional study. Bone. 2020;141:115630.

Murshed M. 2017. Bone mineralization. Cold Spring Harb Perspect Med doi: 10.1101/cshperspect.a031229.

Nakano T, Tsugawa N, Kuwabara A, Kamao M, Tanaka K, Okano T. High prevalence of hypovitaminosis D and K in patients with hip fracture. Asia Pac J Clin Nutr. 2011;20(1):56-61.

Neve A, Corrado A, Cantatore FP. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol, 2013;228(6):1149-53.

O’Connor E, Molgaard C, Michaelsen KF, Jakobsen J, Lamberg-Allardt CJ, Cashman KD. Serum percentage undercarboxylated osteocalcin, a sensitive measure of vitamin K status, and its relationship to bone health indices in Danish girls. Br J Nutr. 2007;97:661–666.

Owen TA, Aronow MS, Barone LM, Bettencourt B, Stein GS, Lian JB. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures. Endocrinology. 1991;128:1496–504.

Ozuru R, Sugimoto T, Yamaguchi T, Chihara K. Time-dependent effects of vitamin K2 (Menatetretone) bone metabolism in postmenopausal women. Endocrine Journal. 2002;49(3):363-370.

Pettifor JM. Vitamin D deficiency and nutritional rickets in children. In Feldman D, Pike JW, Glorieus FH, editors. Vitamin D. 2nd ed. Boston, Massachusetts: Elsevier Academic Press; 2005. p.1065–1084.

Popko J, Karpinski M, Chojnowska S, Maresz K, Milewski R, Badmaev V, et al. Decreased levels of circulating carboxylated osteocalcin in children with low energy fractures: a pilot study. Nutrients. 2018;10:734.

Rahimi GRM, Bijeh N, Rashidlamir A. Effects of exercise training on serum preptin, undercarboxylated osteocalcin and high molecular weight adiponectin in adults with metabolic syndrome. Exp Physio. 2020 Mar;105(3):449-459.

Rahimi GRM, Niyazi A, Alaee S. The effect of exercise training on osteocalcin, adipocytokines, and insulin resistance: a systematic review and meta-analysis of randomized controlled trials. Osteo Int. 2021;32:213-224.

Robling AG, Turner CH. Mechanical signaling for bone modeling and remodeling. Crit Rev Eukaroy Gene Expr. 2009;19(4):319-38.

Rønn S, Harsløf T, Pedersen S, Langdahl B. Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women. Eur. J. Endocrinol. 2016;175:541–549.

Rubin DA, Holmes SC, Ramirez J, Garcia SA, Shumski EJ, Pamukoff DN. Bone mineral density and its relationship with ground reaction force characteristics during gait in young adults with Prader-Willi Syndrome. Bone Rep. 2023 Dec;19:101700.

Russo CR. The effects of exercise on bone. Basic concepts and implications for the prevention of fractures. Clin Cases Miner Bone Metab. 2009;6:223–8.

Saliba W, Barnett O, Rennert HS, Lavi I, Rennert G. The relationship between serum 25(OH)D and parathyroid hormone levels. Am J Med. 2011;124(12):1165–1170.

Sato Y, Kanoko T, Satoh K, Iwamoto J. Risk factors for hip fracture among elderly patients with Alzheimer’s disease. J Neurol Sci. 2004; 223(2):107–12.

Sato T. Vitamin K2 and Bone Quality. Vitam Trace Elem. 2012:S6. doi:10.4172/2167-0390.S6-001.

Seeman E. Pathogenesis of bone fragility in women and men. Lancet. 2002 May 25;359(9320):1841-50.

Seibel MJ, Robins SP, Bilezikian JP. Serum undercarboxylated osteocalcin and the risk of hip fracture. J Clin Endocrino Metab. 1997;82:717–718.

Sharkey NA, Ferris L, Smith TS, Matthews DK. Strain and loading of the second metatarsal during heel-lift. J Bone Joint Surg. 1995;77(7):1050–1057.

Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv in Nutr. 2012;3(2):182-195.

Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures. and sustains lumbar bone mineral density in osteoporosis. J Bone Min Res. 2000;15:515–521.

Thacher TD, et al. A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. N Engl J Med. 1999;41:563–568.

Sim M, Lewis JR Prince, RL, Levinger I, Brennan-Speranza TC, Palmer C, et al. The effects of vitamin K-rich green leafy vegetables on bone metabolism: A 4-week randomised controlled trial in middle-aged and older individuals. Bone Rep. 2020;12:100274.

Sim M, Strydom A, Blekkenhorst L, Bondonno NP, McCormick R, Lim WH et al. Dietary Vitamin K1 intake is associated with lower long-term fracture-related hospitalization risk: the Perth longitudinal study of ageing women. Food & Func. 2022;13:10642-10650.

Smith JK, Dykes R, Chi DS. The effect of long-term exercise on the production of osteoclastogenic and antiosteoclastogenic cytokines by peripheral blood mononuclear cells and on serum markers of bone metabolism. J Osteoporos. 2016:5925380.

Smith C, Lin X, Scott D, et al. Uncovering the bone-muscle interaction and its implications for the health and function of older adults (the Wellderly project): protocol for a randomized controlled crossover trial. JMIR Res Protoc. 2021;10:e18777.

Solarz K, Kopeć A, Pietraszewska J, Majda F, Słowińska-Lisowska M, Mędraś M. An evaluation of the levels of 25-hydroxyvitamin D3 and bone turnover markers in professional football players and in physically inactive men. Physiol Res. 2014;63(2):237–243.

Sumida S, Iwamoto J, Kamide N, Otani T. Evaluation of bone, nutrition, and physical function in Shorinji Kempo athletes. Open Access J Sports Med. 2012;3:107-114.

Susanto LTM. Serum osteocalcin and bone mineral density in postmenopausal women. Universa Med. 2011;30:155–61.

Szulc P, Chapuy M.C., Meunier P.J., Delmas P.D. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Investig. 1993;91:1769–1774.

Torbergsen AC, Watne LO, Wyller TB, Frihagen F, Strømsøe K, Bøhmer T, et al. Vitamin PK and 25(OH)D are independently and synergistically associated with a risk for hip fracture in an elderly population: A case control study. Clin Nutr. 2015;34:101–106.

Trivedi D.P., Doll R., Khaw K.T. Effect of four monthly oral vitamin D3 [cholecalciferol] supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469.

Tsugawa N, Shiraki M, Suhara Y, Kamao M, Ozaki R, Tanaka K, et al. Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J Bone Min Metab. 2008;26:79–85.

Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP. Colas, but not other carbonated beverages are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. Am J Clin Nutr. 2006 Oct;84(4):936-42.

Välimäki V-V, Alfthan H, Lehmuskallio E, Löyttyniemi E, Sahi T, Stenman U-H, et al. Vitamin D status as a determinant of peak bone mass in young Finnish men. J Clin Endo & Metab. 2004;89(1):76-80.

Vasikaran S, Eastell R, Bruyère O, Foldes AJ, Garnero P, Griesmacher A, McClung M, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. 2011 Feb;22(2):391-420.

Vergnaud P, Garnero P, Meunier P., Bréart G, Kamihagi K, Delmas PD. Undercarboxylated osteocalcin measured with a specific immunoassay predicts hip fracture in elderly women: The EPIDOS study. J Clin Endocrinol Metab. 1997;82:719–724.

Vincente-Rodriguez G, Ara I, Perez-Gomez J, Serrano-Sanchez JA, Dorado C, Calbet JAL. High femoral bone mineral density accretion in prepubertal soccer players. Med Sci Sports Exerc. 2004 Oct;36(10):1789-95.

Vincente-Rodriguez G, Dorado C, Ara I, Perez-Gomez J, Olmedillas H, Delgado-Guerra S, et al. Artistic versus rhythmic gymnastics: effects on bone and muscle mass in young girls. Int J Sports Med. 2007 May;28(5):386-93.

Vu Nguyen, Hong. School-based exercise interventions effectively increase bone mineralization in children and adolescents. Osteoporosis and Sarcopenia. 2018;4: 10.1016/j.afos.2018.05.002.

Waterhouse M, Ebeling PR, McLeod DSA, English D, Romero BD, Baxter C, et al. The effect of monthly vitamin D supplementation on fractures: a tertiary outcome from the population-based, double-blind, randomized, placebo-controlled D-Health trial. Lancet Diabetes Endocrinol. 2023 May;11(5):324-332.

Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The national osteoporosis foundation's position statement on peak bone mass development and lifestyle factors: A systematic review and implementation recommendations. Osteoporos Int. 2016;27:1281-386.

Weiler R, Keen R, Wolman R. Changes in bone turnover markers during the close season in elite football (soccer) players. J Sci Med Sport. 2012;15(3):255–258.

Wein MN, Kronenberg HM. Regulation of bone remodeling by parathyroid hormone. Cold Spring Harb Perspect Med. 2018 Aug 1;8(8):a031237.

Whyte MP. Hypophosphatasia: an overview for 2017. Bone. 2017 Sep;102:15-25.

Yakabe M, Hosoi T, Matsumoto S, Fujimori K, Tamaki J, Nakatoh S, et al. Prescription of vitamin D was associated with a lower incidence of hip fractures. Sci Rep. 2023;13:12889.

Yaegashi Y, Onoda T, Tanno K, Kuribayashi T, Sakata K, Orimo, H. Association of hip fracture incidence and intake of calcium, magnesium, vitamin D, and vitamin K. Eur J Epidemiol. 2008;23:219–225.

Zhou R, Guo Q, Xiao Y, Guo Q, Huang Y, Li C, et al. Endocrine role of bone in the regulation of energy metabolism. Bone Research. 2021;9(25): DOIhttps://doi.org/10.1038/s41413-021-00142-4

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