Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Vitamin A decreases the anabolic bone response to mechanical loading by suppressing bone formation
Visa övriga samt affilieringar
2019 (Engelska)Ingår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 33, nr 4, s. 5237-5247Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Increased vitamin A consumption is associated with decreased cortical bone mass and increased fracture risk in humans. Rodent studies have demonstrated that hypervitaminosis A increases cortical bone resorption, whereas the importance of the effects on bone formation is less well defined. We used an experimental model of increased bone formation by loading of the tibiae to investigate the effect of vitamin A on bone formation. Control [retinol activity equivalents (RAE) 4.5 µg/g chow] or vitamin A (RAE 60 µg/g chow) diets were given to female C57BL/6N mice for 4 wk, after which the tibiae were subjected to axial loading on alternate days for 2 wk, while the diets were continued. Vitamin A inhibited the loading-induced increase in trabecular and cortical bone volume. This was attributed to inhibition of loading-induced increase in osteoblast number and activity, and expression of osteoblastic genes Sp7Alpl, and Col1a1 in cortical bone. Vitamin A, loading, and combination thereof also resulted in site-specific effects on bone composition measured by Raman spectroscopy. In summary, a clinically relevant dose of vitamin A suppresses the loading-induced gain of bone mass by decreasing bone formation. These observations may have implications for regulation of bone mass caused by physical activity and the risk of osteoporosis in humans.—Lionikaite, V., Henning, P., Drevinge, C., Shah, F. A., Palmquist, A., Wikström, P., Windahl, S. H., Lerner, U. H. Vitamin A decreases the anabolic bone response to mechanical loading by suppressing bone formation.

Bone remodeling is a continuous process throughout life that is balanced by bone-forming osteoblasts and bone-resorbing osteoclasts (1, 2). With age, the balance of remodeling is often disrupted, and bone resorption exceeds formation, leading to decreased bone mass and, eventually, osteoporosis and fractures (3–5). Although preventative measures can be taken to delay the onset and magnitude of bone loss (e.g., diet and exercise), bone loss can also be exacerbated by drugs such as glucocorticoids and vitamins such as vitamin A (retinol) if consumed in excess.

Vitamin A is found in foods such as meat, dairy products, and vegetables. A balanced diet is sufficient to maintain the nutritional needs; however, fortification of products as well as supplementation with vitamins leads to an increased risk of hypervitaminosis A and is becoming an increasing problem (6). Excess vitamin A consumption and elevated serum retinol levels have been associated with increased bone fragility and fracture risk in humans (7–10). This association indicates that increased vitamin A intake may be a risk factor for secondary osteoporosis.

The current recommended daily allowance for vitamin A consumption in adults is 900 and 700 µg retinol activity equivalents (RAE) per day in men and women, respectively (11). The upper tolerable limit of maximum vitamin A consumption that does not pose ill effects is 3000 µg/d (11). Supplements, whether single-ingredient or multimineral or multivitamin when combined with food or each other, often contain over 100% of the recommended daily allowance of 1 or more nutrients (12). Besides professional athletes (13), the elderly (aged 60 y and over) are the highest users of supplements (12). For this reason, supplementation of vitamin A or constituents high in vitamin A (e.g., liver oil), in addition to an already balanced diet, may exacerbate bone loss.

In experimental rat studies, a 142-fold increase in vitamin A intake (RAE vitamin A 510 µg/g chow) has been illustrated to induce hypervitaminosis A and vitamin A toxicity determined by serum retinol status, reduced food intake, and reduction in weight gain (14–16). In rats receiving oral gavage of a 200–500-fold increase of vitamin A levels (RAE vitamin A 3000–7500 µg/d), spontaneous long-bone fractures have been reported (17). Short-term hypervitaminosis A in rodents decreases cortical bone because of an increased number of osteoclasts on the periosteal bone (14, 17–19) and a decreased number on the endocortical bone (14).

The effects of vitamin A on bone formation have been less well studied. In 2 studies, rats fed hypervitaminosis A diet containing 1700 IU (RAE vitamin A 510 µg/g chow) for 7 d have decreased osteoblast activity and number on the periosteal bone of the femur (15) and on the pericranial side of the calvaria (16). In another study, mice given daily injections of 125 µg/kg of the retinoid Ro 13-6295 for 4 d had a reduced number of osteoblasts with no effect on their activity (19).

Although the doses of vitamin A used in rodent studies are high, they are not necessarily reflective of human consumption in either quantity or duration. More recently, we have shown that a clinically relevant dose of vitamin A (RAE 60 µg/g chow), which is only 13 times higher than control diet, decreased periosteal bone formation after 1 wk and also increased endocortical bone formation after 1 and 4 wk of treatment in mice (20). Thus, via concomitant increase in bone resorption and decrease in bone formation, excess vitamin A can lead to decreased bone strength (14, 21) and increased risk of fractures (8, 9, 22–24).

Bone strength is dependent on size, architecture, and composition. Loading of the skeleton during physical activity leads to recruitment of bone-forming osteoblasts in order to adapt the bones to the applied strain, thereby increasing bone strength (25). Bone is composed of organic (mainly collagen type 1 fibers) and inorganic (hydroxyapatite, calcium, phosphate) compounds that reflect the quality of the bone. Axial mechanical loading of the tibia in rodents is the gold standard of studying bone response to load (26). It is also a good model of impact sports and can be used against a background of various dietary supplements. Often it is noted that the opportune time to enhance bone strength and reduce the risk of fractures later in life is during childhood and puberty; however, implementation of exercise in postmenopausal women has also shown increases in bone mineral density (BMD) at the lumbar spine and femoral neck (27–31).

We hypothesized that a clinically relevant dose of vitamin A may inhibit the bone-forming effects of mechanical loading in mice, in addition to activation of bone resorption. Therefore, we assessed the loading response in bone with and without prior and concurrent treatment with a clinically relevant dose of vitamin A.

Ort, förlag, år, upplaga, sidor
Federation of American Societies for Experimental Biology , 2019. Vol. 33, nr 4, s. 5237-5247
Nyckelord [en]
osteoblasts retinoids, physical activity, Raman spectroscopy
Nationell ämneskategori
Ortopedi
Identifikatorer
URN: urn:nbn:se:umu:diva-158085DOI: 10.1096/fj.201802040RISI: 000462888500049PubMedID: 30668919OAI: oai:DiVA.org:umu-158085DiVA, id: diva2:1304894
Forskningsfinansiär
VetenskapsrådetTillgänglig från: 2019-04-15 Skapad: 2019-04-15 Senast uppdaterad: 2019-04-15Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Förlagets fulltextPubMed

Sök vidare i DiVA

Av författaren/redaktören
Wikström, Pernilla
Av organisationen
Patologi
I samma tidskrift
The FASEB Journal
Ortopedi

Sök vidare utanför DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 40 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf