Thegrossskeletalchangesdependontheseverityoftherachiticprocess;itsduration;and,inparticular,thestressestowhichindividualbonesaresubjected.Duringthenonambulatorystageofinfancy,theheadandchestsustainthegreateststresses.Thesoftenedoccipitalbonesmaybecomeflattened,andtheparietalbonescanbebuckledinwardbypressure;withthereleaseofthepressure,elasticrecoilsnapsthebonesbackintotheiroriginalpositions(craniotabes). Anexcessofosteoidproducesfrontal bossing andasquaredappearancetothehead.Deformationofthechestresultsfromovergrowthofcartilageorosteoidtissueatthecostochondraljunction,producingthe“rachitic rosary.” Theweakenedmetaphysealareasoftheribsaresubjecttothepulloftherespiratorymuscles,causingthemtobendinwardcreatinganteriorprotrusionofthesternum(pigeon breast deformity). TheinwardpullatthemarginofthediaphragmcreatestheHarrison groove, girdlingthethoraciccavityatthelowermarginoftheribcage.Thepelvismaybecomedeformed.Whenanambulatingchilddevelopsrickets,deformitiesarelikelytoaffectthespine,pelvis,andlongbones(e.g.,tibia),causing,mostnotably,lumbar lordosis andbowing of the legs (
Fig.8.21C
Inadultswithosteomalacia, thelackofvitaminDderangesthenormalboneremodelingthatoccursthroughoutlife.Thenewlyformedosteoidmatrixlaiddownbyosteoblastsisinadequatelymineralized,producingtheexcessofpersistentosteoidthatischaracteristicofosteomalacia.Althoughthecontoursofthebonearenotaffected,theboneisweakandvulnerabletogrossfracturesormicrofractures,whicharemostlikelytoaffectvertebralbodiesandfemoralnecks.Onhistologicexamination,theunmineralizedosteoidcanbevisualizedasathickenedlayerofmatrix(whichstainspinkinhematoxylinandeosinpreparations)arrangedaboutthemorebasophilic,normallymineralizedtrabeculae.
Nonskeletal Effects of Vitamin D. As mentioned earlier, the vitamin D receptor is present in various cells and tissues that do not participate in calcium and phosphorus homeostasis. In addition, macrophages, keratinocytes, and tissues such as breast, prostate, and colon can produce 1,25-dihydroxyvitamin D. It appears that pathogen-induced activation of Toll-like receptors in macrophages causes increased expression of vitamin D receptor as well as increased local synthesis of 1,25-dihydroxyvitamin D. This causes activation of vitamin-D-dependent gene expression in macrophages and other neighboring immune cells. The net effect of these changes on the immune response remains to be determined. It appears that in some patients with tuberculosis, vitamin D supplements increase lymphocyte counts and enhance the clearance of Mycobacterium tuberculosis. It has also been reported that low levels http://ebooksmedicine.net
Inadequate synthesis Impaired wound healing Periosteum and joints of osteoid
Fig. 8.22 Major consequences of impaired formation of collagen caused by vitamin C deficiency.
of 1,25-dihydroxyvitamin D (<20 ng/mL) are associated with a 30% to 50% increase in the incidence of colon, prostate, and breast cancers, but whether or not vitamin D supplementation can reduce cancer risk has not been firmly established.