Supplementary webappendixThis webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.

Supplement to: Zebaze RMD, Ghasem-Zadeh A, Bohte A, et al. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 2010; 375: 1729–36.

Diminution in total, cortical and trabecular bone mass across age were derived as follows: The total bone mass within the volume of interest at a time (t), (Mt), is the sum of cortical mass (X) and trabecular mass (Y): M t (CDt * CVt ) (TDt * TVt ) where CDt and CVt are cortical density and volume, TDt and TVt are the trabecular density and volume respectively at time (t). The diminution in total bone mass (∆Mt, t+1) between times (t) and (t+1) is M t , t1 M t M t1 As the age-related enlargement of the medullary cavity in bone specimens was due to trabecularization, we attributed the age-related diminution of cortical volume to intracortical remodelling producing cortical remnants in vivo plus void (pores). The cortical mass lost by trabecularization (

X trab t , t1

) is a function of the diminution in CV, CD, TV & TD between times

(t) and (t+1) and is:

X trab t , t1

((CDt * (CVt CVt1)) (TDt1 * (CVt CVt1))

Change in cortical mass (∆CMt,t+1) between times (t) and (t+ 1) due to porosity without the production of cortical remnants is: CM t, t1 (CDt TDt1) * (CVt CVt1) Intracortical remodelling between (t) and (t+1) produces cortical remnants at (t+1) which appear ‘trabecular’ ( CTrt1) and are estimated as CTrt1 (CVt CVt1) * TDt1 The proportion of ‘trabecular’ bone ( PCTrt1) of cortical origin in the marrow at (t+1) is

PCTrt1 100* CTrt1 /(TDt1 * TVt1) expressed as a percentage. The diminution in cortical mass (Xt,t+1) between (t) and (t+1) = the sum of the diminution of cortical mass produced by porosity causing trabecularization (cortical remnants) and the diminution in cortical mass in the remaining compact cortex produced by increasing porosity without production of cortical remnants. It is computed as

X t, t1 ((CVt1) * (CDt CDt1)) X trab t , t1

. The diminution in trabecular mass (∆Yt, t+1)

between (t) and (t+1) is the difference between the diminution in total bone mass and the diminution in cortical mass and is Yt , t1 M t, t1 X t, t1

Supplementary figure 1

1

Supplementary figure 2

2

Supplementary figure 3

3

Supplementary figure 4

4

Supplementary figure 4

Legend for supplementary figures & videos

Micrograph (1). Micrograph of a specimen at the mid-shaft of the femur in a 90 year old woman. The solid arrow shows largecoalescent intracortical pores in a structure of trabecular-like appearance within an intact endocortical surface. This suggest that this‘trabecular like structure is not likely to be the result of endocortical resorption

The insert shows that ~ 2 mm (~ 40%) out of the 5 mm thickness of the cortex is eroded by intracortical remodelling rather thanendocortical resorption producing trabecularization. The mid-shaft is devoid of trabeculae and so that this cannot be trabecular bone ofgrowth-plate origin.

Micrograph (2). It is unlikely that the large coalescent pores adjacent to the periosteum in this 90 year old women originate fromremodelling on the endocortical surface.

Micrographs (3) The cross section at the sub-trochanteric region in a 29 year old woman has normal cortical architecture free of largepores and trabecularization. Compare the cross section to that of the 78 and 90 years old women shown in figure 4 a & d in the text.

Figure (4). Micrographs from the subtrochanteric region. Low BMD is not synonymous with high porosity. A 72 year old woman with17% porosity (A1) and 90 year old woman with 46% porosity (A2) yet both have similar T-scores (of -2.57 SD and -2.56 SDrespectively). A 72 year old woman (B1) with osteopenia (T-score -1.14 SD yet porosity is 15%, similar to a 29 year old woman with highBMD (T-score 1.92 SD, 14% porosity) (B2). Normal BMD is not synonymous with low porosity. A 67 year old women with normalBMD (T-score = - 0.2 SD) has 24% porosity (C). Figures 6D illustrates that 50% of specimens are discordant for BMD and porosity;in 6 specimens, porosity is high yet BMD T score is > -1.0 SD) while in 5 specimens porosity is minimal yet BMD is < -1 SD.

Videos (axial and coronal views). This is a reconstruction of the intracortical pores at 12 microns resolution in a block of bone (3 x 3x 3 cm) from the subtrochanteric region. From section to section pores coalesce but remain intracortical and most do not communicatewith marrow space along the 3 cm axial or coronal sections. In the coronal view, the chaotic architecture of cortical remnants producedby intracortical remodelling is apparent.