OBJECTIVE: To examine the effects of prolonged preferential weight bearing (PWB) and reduced ambulation (RA) on hoof lamellae using a nonpainful in vivo experimental model. METHODS: 12 healthy Standardbred horses were housed in stocks continuously for 92 hours. A platform shoe was placed on 1 forelimb in the PWB group (n = 6) to increase the load on the supporting limb (SL) by approximately 10% bodyweight, whereas the RA group (n = 6) had normal weight bearing. Archived healthy horse (n = 8) samples were used as controls. Histomorphometry and histochemistry (terminal deoxynucleotidyl transferase dUTP nick-end labeling [TUNEL], caspase-3, and targeting protein for Xenopus kinesin-like protein [TPX-2]) results were analyzed using mixed-effects linear regression. RESULTS: Lesions in multiple limbs from the PWB and RA groups included secondary epidermal lamellae elongation, cell death (mostly TUNEL-positive, caspase-3-negative parabasal keratinocytes), and basal cell proliferation (TPX-2 positive). Lesions were most severe in the PWB group SL, with significant increases (vs control) in mean (95% CI) primary epidermal lamellar (PEL) length (3.7 [95% CI, 3.5 to 3.8] mm vs 3.2 [95% CI, 2.9 to 3.4] mm
P <
.001), secondary epidermal lamellae length (281 [95% CI, 235 to 327] µm vs 185 [95% CI, 155 to 215] µm
P <
.001), TUNEL count (45 [95% CI, 30 to 60] vs 4 [95% CI, 2 to 5] positive cells/PEL
P <
.001), and TPX-2 count (116 [95% CI, 46 to 186] vs 5 [95% CI, 3 to 6] positive cells/PEL
P <
.002). Both TUNEL- and TPX-2-positive cell counts were increased in the RA group forelimbs versus control (P <
.05). CONCLUSIONS: Restriction of normal ambulation, even in the absence of increased weight bearing, caused lamellar parabasal keratinocyte death and structural derangement of lamellae. CLINICAL RELEVANCE: Promoting ambulation, not just limb load relief, may be a critical strategy for preventing SL laminitis.