Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. This in turn stimulates PTH production, which (1) activates renal α1-hydroxylase, increasing the amount of active vitamin D and calcium absorption; (2) mobilizes calcium from bone; (3) decreases renal calcium excretion; and (4) increases renal excretion of phosphate. Thus, the serum level of calcium is restored to near normal, but hypophosphatemia persists, so mineralization of bone is impaired or there is high bone turnover.
An understanding of the morphologic changes in rickets and osteomalacia is facilitated by a brief summary of normal bone development and maintenance. The development of flat bones in the skeleton involves intramembranous ossification, whereas the formation of long tubular bones proceeds by endochondral ossification. With intra-membranous bone formation, mesenchymal cells differentiate directly into osteoblasts, which synthesize the collagenous osteoid matrix on which calcium is deposited. By contrast, with endochondral ossification, growing cartilage at the epiphyseal plates is provisionally mineralized and then progressively resorbed and replaced by osteoid matrix, which undergoes mineralization to create bone (
Fig. 8.21A
MORPHOLOGYThe basic derangement in both rickets and osteomalacia is an excess of unmineralized bone matrix. Thechangesthatoccurinthegrowingbonesofchildrenwithrickets,however,arecomplicatedbyinadequateprovisionalcalcification http://ebooksmedicine.net
Fig. 8.21 Rickets.(A)Normalcostochondraljunctionofayoungchild.Notecartilagepalisadeformationandorderlytransitionfromcartilagetonewbone.
(B)Rachiticcostochondraljunctioninwhichthepalisadeofcartilageisabsent.Darkertrabeculaearewell-formedbone;palertrabeculaeconsistofuncalcifiedosteoid.(C)Notebowingoflegsasaconsequenceoftheformationofpoorlymineralizedboneinachildwithrickets.(B, Courtesy of Dr. Andrew E. Rosenberg, Massachusetts General Hospital, Boston, Massachusetts.) ofepiphysealcartilage,derangingendochondralbonegrowth.Thefollowingsequenceensuesinrickets:
Persistenceofdistorted,irregularmassesofcartilage,manyofwhichprojectintothemarrowcavity
Disruptionoftheorderlyreplacementofcartilagebyosteoidmatrix,withenlargementandlateralexpansionoftheosteochondraljunction(
Fig.8.21B
Abnormalovergrowthofcapillariesandfibroblastsinthedisorganizedzoneresultingfrommicrofracturesandstressesontheinadequatelymineralized,weak,poorlyformedbone