Poster Session - Bone Biology - Hall E 47th Annual Meeting, Orthopaedic Research Society, February 25 - 28, 2001, San Francisco, California 0477

ESTROGEN DEPLETION IS ASSOCIATED WITH CHANGES IN THE REGIONAL VARIATION OF COMPACT BONEDENSITY

+*Les, C (A-HFH Grant Development Fund); *Spence, C; *Planitkar, S; *Nakoneczny, A; **Turner, A+*Henry Ford Hospital, Detroit, MI. Bone and Joint Center, 2015 ERB, Henry Ford Hospital, 2799 W. Grand Blvd, Detroit, MI 48202, (313) 916-3166, Fax: (313)

916-8064, les@bjc.hfh.edu

INTRODUCTIONOsteoporosis is characterized by decreased bone mass and deterioration

of bone tissue microarchitecture, and is associated with increased risk ofvertebral, hip, and wrist fractures (1), a risk that is not adequately predicted bycurrent screening protocols (e.g., DXA, QCT) (2). While much of the loss ofstructural integrity that occurs with postmenopausal decreases in circulatingestrogen has been attributed to in cancellous bone losses (3,4), recent workhas also suggested a substantial contribution of compact bone loss to changesin structural properties (5,6).

Earlier work has suggested that both the geometry (7) and distribution ofmaterial properties (8) in bone tend to have the effect of causing the structureto preferentially bend in certain directions under normal loading conditions.Furthermore, a recent finite element study (9) determined that a relativelysmall change in bone material properties, strategically placed in a localizedregion, had effects on the mechanical behavior of the structure that weredisproportionate to the amount of bone loss that was modeled. If there aresignificant alterations in the distribution of mechanical properties of the bone,the structural properties of the bone may well change substantially withoutthere being significant changes in clinically-measurable indices of overallbone mineral density.

Our objective in this study was to characterize the pattern of compactbone density change in an ovine model of postmenopausal osteopenia. Ourhypothesis was that the distribution of bone density would changesignificantly with estrogen depletion.METHODS

Under institutional animal care and use guidelines, 5-year-old retiredbreeder Warhill ewes were ovariectomized (OVX, N=6) or subjected to asham surgery (SHAM, N=10) in the spring of the year. The animals werekept under dry lot conditions for one year, after which they were sacrificed.The left radius/ulna was harvested and stored at -20oC until analysis. Thecentral 4cm of the diaphysis was cut on a precision band saw (Exakt) into oneradioulnar and 4 radial sectors (Fig.1). Volumes were determined byweighing the specimens in air and water, and the specimens were then dried at100oC overnight, followed by ashing in a muffle furnace at 800oC for 24hours. Ash weights were determined, and ash densities (ρρρρa) calculated. Arepeated-measures ANOVA was performed on ρa, with sheep as the subject,and anatomic sector and treatment (OVX or Sham) as categorical variables.

Fig.1: Cross-section of ovine radius/ulna at proximal diaphysis, with divisionsbetween sectors outlined in white. Cranial is to the upper right, lateral is tothe upper left.

RESULTSNo significant overall effect of treatment (p=0.868, power=0.05) could

be found in ρa. There was a significant effect of anatomic location (p<0.001,cranial sectors having significantly higher ρa than caudal ones). There was asignificant interaction between treatment and anatomic location (p=0.009), in

which there was a trend toward lower ρa with estrogen depletion at thecraniomedial and caudomedial sectors (p<0.12), and a significant increase inρa (p=0.01) at the caudolatero-ulnar sector (Fig.2).

Ash Density, gm/ccOvine Radius/Ulna

1.01.11.2

ShamOVX

Cranial

Lateral

Fig.2: Distribution of ρa in the sham-operated and OVX radius/ulna. Radiusis proportional to ρa, angle is proportional to anatomic site.

DISCUSSIONIn this system, our data suggest that the change in ρa in early of estrogen

depletion is neither concentric nor random, and may not even be negative. Ineffect, ρa appeared to be redistributed without a concomitant change in overalldensity. Since material properties such as elastic modulus and strength areoften related to ρa by a power function (10), the mechanical consequences ofeven relatively small but localized changes in ρa could significantly alter thedirection and magnitude of structural bending under normal loadingconditions.

A global change in signal (e.g., estrogen depletion) resulting in a non-global effect (e.g., change in regional distribution of ρa) must postulate a non-uniform intermediary step. The mechanism for these changes cannot bedetermined from these data, but are obviously related to the characteristics ofthe increase in bone turnover that is seen with estrogen depletion. Futurework to clarify the mechanisms of this effect should concentrate on thedistribution of remodeling patterns that accompany estrogen depletion.REFERENCES1. Wasnich RD: in Primer on the metabolic bone diseases and disorders ofmineral metabolism3rd, ppg 249-251. Ed by MJ Favus. Philadelphia,Lippencott-Raven, 1996. 2. Greenspan SL, Myers ER, Maitland LA, et al: JAMA 271(2): 128-133, 1994. 3. Bergot C, Laval-Jeantet A-M, Preteux F,Meunier A: Calicif Tiss Int 43: 143-149, 1988. 4. Amling M, Herden S, PoslM, et al: J Bone Min Res 11(1): 36-45, 1996. 5. Bell KL, Loveridge N,Power J, et al.: J Bone Min Res 14(1): 111-119, 1999. 6. Spadaro JA, WernerFW, Brenner RA, et al. J Orthop Res 12: 211-218, 1994. 7. Bertram JEA,Biewener AA: J. Theor Biol 131: 75-92, 1988. 8. Les CM, Stover SM,Keyak JH, et al.: J Biomech 30(4): 355-361, 1997. 9. Oden ZM, SelvitelliDM, Bouxsein MLJ Orthop Res 17(5): 661-667, 1999. 10. Les CM, KeyakJH, Stover SM, et al.: J Orthop Res 12: 822-833, 1994.

**Colorado State University, Ft. Collins, CO.