Reproductive Hormonesp 192 Kanis 1994 As aging bonesweaken they reach - PDF document

1 Reproductive Hormones,p. 192) (Kanis 199
Reproductive Hormones,p. 192) (Kanis 1994). As aging bonesweaken, they reach a point (i.e., frac-ture threshold) at which even minorstress can cause fractures. Adolescent Bone Development and Alcohol Achieving an optimal peak bone massduring adolescence may reduce a per-s risk for developing osteoporosis(i.e., bone loss with fracture) later inwithstand a longer duration and greaterlevel of bone loss before reaching thefracture threshold. Although peakbone mass appears to be largely undergeneticcontrol (Pocock et al. 1987),it can be influenced by hormonal,nutritional, environmental, andA significant proportion of thebone. A nationwide survey of morefound that 63 percent of seniors had been drunk at least once and 51percent had consumed alcohol in the month before the survey. Mostrespondents had consumed alcoholfor the first time before age 13 (ArriaResults of experiments using laboratory animals suggest potentialtion during adolescent bone growth.to young, rapidly growing rats signifi-cantly reduced bone growth, volume,density, and strength (Hogan et al.1997; Sampson et al. 1996, 1997).The longitudinal growth rate and the rate of proliferation of cells in the growing region near the ends of long bones (i.e., growth plates)administration. If those effects occurdecrease bone mass. The decreasedbone mass that occurs from early,could result in increased fracture andearly onset of osteoporosis. on Hormones that Regulate Bone In addition to providing structuralsupport, bone is a major storagefrom ingested food, and the kidneysexcrete excess calcium. An adequatebloodstream is required for theproper functioning of nerves andconcentration and responds throughand local growth factors to regulatethe distribution of calcium betweendisrupt this balance by affecting the hormones that regulate calciummetabolism as well as the hormonesindirectly (e.g., steroid reproductivehormones and growth hormone[GH]) (Sampson 1997). Calcium-Regulating HormonesParathyroid Hormone. Parathyroidhormone (PTH) is secreted into thebloodstream by four small glands locatedbehind the thyroid gland in the neck.The hormone, which is produced inresponse to decreasing levels of calciumspecialized bone cells called osteoclasts(see figure 3, p. 193). Osteoclasts dissolvesmall areas of bone, releasing calciuminto theblood. (The role of osteoclastsin bone remodeling is discussed inthes Effects on BoneRemodeling, p. 193) In addition, PTHinhibits the excretion of calcium by thekidney and activates vitamin D, whichpromotes the absorption of calcium fromthe intestine. The resulting increase incalcium levels eventually inhibits furtherPTH production.Short-term alcohol consumptionincreases PTH secretion, possibly bycausing calcium to leave body fluids(e.g., blood) and flow into cells(Williams et al. 1978). Laitinen andcolleagues (1991) administered intox-icating doses of alcohol over a 3-hourperiod to men and women who werereceiving approximately 5 to 11 standardLevels of PTH declinedperiod and rose over the next 9 hours,eventually exceeding levels measuredbefore alcohol consumption. Urinarycal

2 cium excretion increased duringdecreased
cium excretion increased duringdecreased. Long-term heavy drinkingwas associated with low blood calciumlevels (Laitinen et al. 1991). Alcohol 191 Figure 1 A section of the upper endof the long bone of the thigh (i.e., the CT 1more than two standard drinks per day for menmore than 10 drinks per day, more than one-half at least three times the legal limit for driving inany State. did not result from reduced PTHsecretion and also suggest that alcoholadministration impaired the abilityofthe parathyroidglands to increasePTH production in response to thepresence of hypocalcemia (Laitinen Calcitonin. Specialized cells in thethyroid gland produce calcitonin, ahormone that protects the skeletonfrom calcium loss by inhibiting osteo-clast activity. In contrast to the actionof PTH, calcitonin increases thelowers the level of calcium in theblood. Calcitonin levels increase onlybriefly during acute and short-termalcohol consumption (Balabanova etal. 1989; Williams et al. 1978). Thesignificance of this effect is uncertain. Vitamin D. Vitamin D increases intesti-nalabsorption of dietary calciumand has a function in normal bonemetabolism.Vitamin D is formed in the skin through the action ofas liver, eggs, and milk. The vitaminbecomes physiologically active onlyliver and kidneys. Alcoholics normallyhave low levels of activated vitaminD, along with low levels of theproteins that bind with vitamin Dto protect it during transport withinthe blood (Bikle et al. 1993). VitaminD levels are especially low in thepresence of alcoholic liver diseasealcohol-induced decrease in activatedvitamin D results in decreased absorp-levels quickly return to normal follow-ingabstinence (Krawitt 1975). Reproductive Hormones Osteoporosis can develop in post-as well as in men with inadequategonadal function (Jackson et al.1987). Alcoholic men frequentlyhave decreased levels of the malesteroid hormone testosterone(produced mainly in the testes), increased metabolic conversion of testosterone (produced in theovaries and adrenal glands) to thefemale steroid hormone estradiol(Diamond et al. 1989; Gavaler and Van Thiel 1992). Because estrogen deficiency is a major con-tributing factor for the develop-ment of osteoporosis, alcohol mightindirectly affect bone throughestrogen. Estrogen replacementreduces a womans risk of develop-ing postmenopausal osteoporosis. In addition, moderate alcoholconsumption has been reported to increase estrogen levels in theblood. A review of published researchon alcohol and estrogen (Purohit1998), however, concluded thatno more than one drink per day for women) does not appear to havea significant effect on levels of estra-diol, the most potent of the estrogens. Effects of Moderate AlcoholConsumption Studies show a relationship betweenalcohol and bone loss. However, a fewconsumption may help reduce osteo-porosis and decrease fracture risk inpostmenopausal women (Holbrookand Barrett-Connor 1993; Laitinen etal. 1991). For example, in a study ofmore than 14,000 subjects, NavesDiaz and colleagues (1997) reportedconsume alcohol on more than 5 daysper week had a redu

3 ced risk of verte-bral deformity compare
ced risk of verte-bral deformity compared with thoseper week.Two recent studies investigated thesumption on rats following surgicalremoval of their ovaries (i.e., ovariec-tomy) to mimic menopause. In onestudy (Fanti et al. 1997), rats wereadministered doses of alcohol equiva-lent to 18 percent of their total dietarycaloric intake for 3 weeks. Sampsonand Shipley (1997) administered theequivalent of two standard drinks, aspreviously defined, per day for 6weeks. In both studies, ovariectomizedrats exhibited decreased bone densityand bone volume compared withnonovariectomized rats. However,these changes were not significantlyaffected by alcohol administration.Although Fanti and colleagues (1997)found fewer osteoclasts in ovariec-tomized alcohol-fed animals, thisfinding was not reflected in decreasedbone volume. Therefore, neitherbone quality. Growth Hormone Growth hormone, secreted by thepituitary gland, is important in bonegrowth and remodeling. Growth hor-mone exerts its effects largely througha hormone called insulin-like growth 192 Figure 2 The effect of alcohol on themicroscopic structure of long bones CC2b Alcohol 193 factor 1 (IGF-1), which is producedin the liver and other organs (seearticle by Dees and colleagues, pp.169). Levels of IGF-1 are signif-icantlyreduced in alcohol-fed animalsuntil 7 months of age (Sampson etThe aforementionedfindings might explain the greatlyreduced rates of longitudinal growthand the proliferation of certain celltypes in the growth plates of young,rapidly growing animals (Sampsonet al. 1997). The levels of IGF-1 inbut bone deficiencies resulting frompossibly through a mechanism inde-pendent of growth factors. Alcohol on Bone Remodeling Remodeling occurs in small, circum-scribed areas scattered on the surfaceof the bone. Osteoclasts (see figure3) erode a cavity on the bone surfacein a process known as resorption.When the resorption cavity is com-plete, the osteoclasts disappear, thefloor of the cavity is smoothed off,and a thin layer of matrix or cementosteoblasts) (see figure 4) fill thenewly formed cavity with new bone.Local imbalance of bone remodelingcan occur when osteoclasts erodecavities that are too deep or whenosteoblasts lay down layers of newbone which are too shallow. It isbone remodeling result from improperbone formation or overactive osteo-clast resorption.Schnitzler and Solomon (1984)reduced bone formation and increasedbone resorption. In a study of menwho were daily drinkers and whohad osteoporosis of unknown origin,De Vernejoul and colleagues (1983)found a markedly reduced mean wallthickness (i.e., the thickness of the newly formed structural unitduring remodeling), whiching the quantity of resorbed bone.Based on their calculations, DeVernejoul and colleagues theorizedthat alcoholic osteoporosis is charac-terized by decreased bone formationbut normal levels of resorption. A microscopic analysis of bonetissue from men with osteoporosis(Chappard et al. 1991) confirmeddelayed and impaired osteoblastTo determine whether alcohol has a direct effect on osteoblasts,researchers measured levels ofoste

4 ocalcin, a protein secreted bymeasure of
ocalcin, a protein secreted bymeasure of osteoblast function.Using in vitro preparations of osteo-blasts from rats, most investigatorsreported a decrease in osteocalcinlevels in response to alcohol admin-decreases osteoblastic activity (Penget al. 1991). Microscopic studies ofbone tissue from rats demonstrateddecreased trabecular bone volume,decreased numbers of osteoblasts,and decreased rates of bone form-ation, indicating impaired bonewith other characteristics indicativeof osteoporosis (Sampson 1998;Sampson et al. 1997). In addition,the amount of trabecular surfacecovered by active osteoblasts was significantly reduced in alcohol-fedosteoblast proliferation. Wall thick-ness, another measure of osteoblastactivity, was reduced by 52 percentin alcohol-fed animals compared withanimals not administered alcohol(Dyer et al. 1998). These findingsagree with in vitro studies thatChavassieux et al. 1993; Friday and Howard 1991). Overall, alcoholappears to suppress osteoblastfunction in adults, resulting indecreased bone formation. Summary Chronic alcohol consumption hasharmful effects on bone develop-s action on young, growingalcohol reducescan result in relatively weak adult bonesthat are more susceptible to fracture.are modulated by hormones, including Figure 4 Microscopic view of bone-forming cells, or osteoblasts (arrow), ooc 3thirties in a human. Figure 3 Microscopic view of abone-resorbing cell, or osteoclast 194 and growth hormone,as well as by othersubstances, such asvitamin D. However,these interactionsdo not appear to be themajor mecha-s effectson adult bone.Results of human and indicate that alcohol directlys effect on bone-resorbingcells, however, is uncertain. Additionalresearch is needed to explain all of  References AD.H. The effects of alcohol abuse on the healthof adolescents. Alcohol Abuse and AdolescentHealth 15:52Ð57, 1991.BG. Die Rolle der Calcium-Homšbei der Toleranzentwicklung nach Drogen-und Beitrage zur Gerichtliche Medezin 47:379Ð383, 1989.B, D.D. Alcohol-induced bone disease. In:Simopoulos, A.P. and Galli, C., eds. Osteoporosis:Nutritional Aspects. Basel, Switzerland: Karger,Ð79.CAsis and osteoporosis in men: A light and scanning Journal of Studies on 52:269Ð274, 1991.C, P.; SERRE, C.M.; VERGNAUD, P.;D, P.D.; AND, P.J. In vitro evalua-cells. Bone and Mineral , D.;K Clinical Orthopaedics andRelated Research 179:107Ð115, 1983.D, T.; STIEL, D.; LUNZER, M.; WILKINSON, S. Ethanol reduces bone forma-tion and may cause osteoporosis. American Journalof Medicine 86:282288, 1989.DUCKENDAHLH.W. Alcohol consumption inhibits osteoblasticcell proliferation and activity in vivo. Alcohol 16(4):337Ð342, 1998.F, P.; MONIER, M.C.; GENG, Z.;C, D.; AND, H.H. Moderatelyhigh consumption of ethanol suppresses bone Alcoholism: Clinical andExperimental Research 21:11501154, 1997.Fhuman bone cell proliferation and function in vitro. Metabolism , D.H. The associa- Alcoholism: Clinical and Experimental 16(1):87Ð92, 1992.H, N. Alcohol consumption by youngactively growing rats: A study of cortical bone his- Alcoholism: Clinical and Experime

5 ntal Research ,E. A British Medical Jour
ntal Research ,E. A British Medical Journal 306:1506Ð1509, 1993.JILLANUEVA, A.R.; Journal 65:53Ð58, 1987.K, J.A. Osteoporosis . Oxford, England: BlackwellScience, 1994.K, R.F.; FEthanol inhibits human osteoblastic cell prolifera- Alcoholism: Clinical and ExperimentalResearch 20:572Ð578, 1996.Kduodenal calcium transport. Journal of Laboratoryand Clinical Medicine 85:665Ð671, 1975.LT, R.; KARONEN, R.;, M. Transienthypoparathyroidism during acute alcohol intoxi- New England Journal of Medicine 324:721Ð727, 1991.L, M. Mechanisms of hypocalcemiaand markers of bone turnover in alcohol-intoxi- Bone and Mineral 24:171Ð179,1994.Mof adolescent girls. Nutrition Today March/April:Ð24, 1991.MEATON Journal of Dental Research 74:698Ð701,1995.Alcoholism. Alcohol Alert 16: Moderate Drinking .ÕNA.J. The influence of alcohol consumption on therisk of vertebral deformity. Osteoporosis Inter-national 7(1):65Ð71, 1997.PR.P. Lower serum osteocalcin in ethanol-fed rats. Journal of Bone and Mineral Research 6:107Ð115,1991.PY, M.G.; S, S.Genetic determinants of bone mass in adults: A Journal of Clinical Investigation 80:706Ð710, 1987.Pestrogen levels in postmenopausal women: A Alcoholism: Clinical and ExperimentalResearch 22(5):994Ð997, 1998.Sregulating hormones. Alcoholism: Clinical andExperimental Research 21:400Ð403, 1997.Son adult and aged bone: A histomorphometric Alcoholism: ,D. Moderate Alcoholism: 21:1165Ð1168, 1997.S, B. Alcohol consumption inhibitsbone growth and development in young actively Alcoholism: Clinical and Exper-imental Research 20:1375Ð1384, 1996.S, B. Alcohol consumption by youngactively growing rats: A histomorphometric study Alcoholism: Clinical andExperimental Research 21(2):352Ð359, 1997.S, V.A.; BOOE, T.H. The effect of alcohol con-sumption on adult and aged bone: Composition, Alcoholism: Clinical and ExperimentalResearch ,L. Bone South African MedicalJournal 66:730Ð734, 1984.W, W.J. Effect of ethanol on parathy-roid hormone and calcitonin secretion in man. Proceedings of the Society for Experimental Biologyand Medicine 159:187Ð191, 1978. 190 s Harmful Effects H. Wayne Sampson, Ph.D. Long-term alcohol consumption can interfere with bone growth and replacement of bone tissue(i.e., remodeling), resulting in decreased bone density and increased risk of fracture. These effectsmay be exerted directly or indirectly through the many cell types, hormones, and growth factorsthat regulate bone metabolism. Alcohol consumption during adolescence reduces peak bone massand can result in relatively weak adult bones that are more susceptible to fracture. In adults, alco-hol consumption can disrupt the ongoing balance between the erosion and the remodeling ofbone tissue, contributing to alcoholic bone disease. This imbalance results in part from alcohol- EYWORDS Bone is a living tissue that continues Bone Structure and Growth in a hard matrix of protein fibers andcalcium crystals. There are two typesof bone. Cortical bone, which islayer of bones and the shafts of thefigure 1). Cancellous bone, which is a porous meshwork of thin plate