Changes in the skeletal dimensions of the digits of the thoracic limb of Holstein cows after maturation.

The 12 left digits of the thoracic limb of Holstein female cows were obtained from a slaughterhouse, and 13 linear measurements of skeletal specimens of the digits of the thoracic limb were used in this study. Bivariate plots, regressions and correlation analyses were performed to assess the relationships between osteometric data and age, and between osteometric data and body size. The geometric mean (GM) of the metacarpal size was used as a proxy of body weight. The results of the regression analysis demonstrated that the length and the width of the distal phalanx were significantly correlated with age, whereas those of other bones were not. In addition, the correlations of the distal phalanx tended to be higher with age than with the GM of the metacarpal size, and their skeletal measurements tended to be longer in older animals than in younger animals. These findings suggest that the distal phalanx is slightly elongated and enlarged in its solear aspect with increasing age in skeletally mature cows. Moreover, although the side difference in the distal phalanx between the lateral and medial digits did not increase significantly with age, the solear aspect of the distal phalanx tended to be rougher, and deformation of the flexor tubercle tended to be more pronounced in the medial digit compared with the lateral digit. Therefore, in the distal phalanx of the front feet, the skeletal deformation with age and asymmetrical bone development might be related to the pathogenesis of claw horn lesions, as in the hind feet.

The prevalence and ossification pattern of the biphalangeal and triphalangeal lateral toes.

PURPOSE: Biphalangealism of the toes is an exclusively human phenomenon. The aim of this study was to evaluate the development of the lateral toes in childhood by following the ossification pattern of the phalanges. METHODS: Foot radiographs of 913 adults have been evaluated for biphalangealism of 3rd to 5th toe. The pediatric group, aged 6-15 years of age, was assessed for the number of ossification centers in the foot. RESULTS: In adults, the mean prevalence of biphalangealism in the 5th toe was 41.39%, in the 4th toe was 2.15%, and in the 3rd toe was 0.48%. In children, 45% feet had four ossification centers in the 5th toe. The epiphysis center of the middle and distal phalanx was missing. In the 4th toe, four centers were present in of 2.47% of cases. Those values are similar to the prevalence of the biphalangeal toes in adult population. The remaining toes had 5 or 6 ossification centers. In the 5-center toe, the epiphysis of the middle phalanx was missing. CONCLUSION: A missing distal phalanx epiphyseal ossification center is considered indicative of a biphalangeal toe, and the toes with 5 or 6 ossification centers are indicative of triphalangeal toes. The reason for such evolution of the lateral toes is still debated, but the differences in anatomy most likely have no impact on foot function.

Radiography of the distal extremity of the manus in the donkey foal: Normal images and quantitative characterization from birth to 2 years of age: A pilot study.

This study describes a radiographic survey of the anatomical development of the distal extremity of the manus in the donkey from 0 to 2 years of age. The right distal limb of 10 donkey foals, born in the spring of 2012, underwent radiographs every month for the first 6 months of age and every 3 months during the following 18 months. Latero-medial radiographs with and without barium marker at the coronary band and dorso-palmar radiographs with both front feet in weight bearing were obtained. The distal physis of the third metacarpal bone and the proximal physis of the proximal phalanx (phalanx proximalis) were closed at the mean age of 18.6 months. The distal physis of the proximal phalanx appeared as a clear radiolucent line at 2 weeks of age and was still subtly visible in some donkeys at 24 months. The proximal physis of the middle phalanx (phalanx media) was closed at the mean age of 16.7 months. The distal physis of this phalanx was visible at birth, but closed at 4 days. The distal phalanx (phalanx distalis) was triangular at birth. At the age of 20-21 months, the palmar processes (processus palmares) were both developed. The navicular bone (os sesamoideum distalis) was developed at the mean age of 9 months. The proximal sesamoid bones (ossa sesamoidea proximalia) were seen in continuously development during the 24 months. It seems that the physes in the distal extremity of the manus in the donkey close at an older age than the physes in the horse.

Five- and 10-Year Follow-Up of Nonvascularized Toe Phalanx Transfers.

PURPOSE: The purpose of this study was to evaluate long-term outcomes of nonvascularized toe phalanx transfer. METHODS: We retrospectively reviewed 54 nonvascularized toe phalanx transfers in 29 children with symbrachydactyly. Forty-seven transfers in 24 children were evaluated at 5-year follow-up and 27 transfers in 14 children were evaluated at 10-year follow-up. We recorded the incidence of the early physeal closure and the length of the transferred toe phalanx on plain radiographs at 5- and 10-year follow-up. Growth rate in the first 5 years and the following 5 years were calculated. Function of the metacarpophalangeal joint (motion, stability, and alignment) was also evaluated. RESULTS: The mean age at surgery was 1.5 years. Seven toe phalanges were trimmed because the skin pocket was tight. Five transfers required revision surgery for partial necrosis of the skin pocket. At 5-year follow-up, the physis was closed in 23%, and at 10 years, 78% of physes were closed. The phalanx length was 87% of expected at 5-year follow-up and 71% at 10-year follow-up. Growth rate was 0.83 mm/y in the first 5 years and 0.22 mm/y in the following 5 years. Active motion was rated as good in 24, fair in 7, and poor in 16. Stability and alignment were rated as good in 37 and 33, fair in 8 and 5, and poor in 2 and 9, respectively. CONCLUSIONS: Nonvascularized toe phalanx transfer offered a relatively simple method to lengthen short digits and to provide satisfactory function. The transferred toe phalanges grew at a near-normal rate in the first 5 years, but the growth rate decreased between 5 and 10 years. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Linking bone development on the caudal aspect of the distal phalanx with lameness during life.

Claw horn disruption lesions (CHDL; sole hemorrhage, sole ulcer, and white line disease) cause a large proportion of lameness in dairy cattle, yet their etiopathogenesis remains poorly understood. Untreated CHDL may be associated with damage to the internal anatomy of the foot, including to the caudal aspect of the distal phalanx upon which bone developments have been reported with age and with sole ulcers at slaughter. The primary aim of this study was to assess whether bone development was associated with poor locomotion and occurrence of CHDL during a cow's life. A retrospective cohort study imaged 282 hind claws from 72 Holstein-Friesian dairy cows culled from a research herd using X-ray micro-computed tomography (µ-CT; resolution: 0.11mm). Four measures of bone development were taken from the caudal aspect of each distal phalanx, in caudal, ventral, and dorsal directions, and combined within each claw. Cow-level variables were constructed to quantify the average bone development on all hind feet (BD-Ave) and bone development on the most severely affected claw (BD-Max). Weekly locomotion scores (1-5 scale) were available from first calving. The variables BD-Ave and BD-Max were used as outcomes in linear regression models; the explanatory variables included locomotion score during life, age, binary variables denoting lifetime occurrence of CHDL and of infectious causes of lameness, and other cow variables. Both BD-Max and BD-Ave increased with age, CHDL occurrence, and an increasing proportion of locomotion scores at which a cow was lame (score 4 or 5). The models estimated that BD-Max would be 9.8mm (SE 3.9) greater in cows that had been lame at >50% of scores within the 12mo before slaughter (compared with cows that had been assigned no lame scores during the same period), or 7.0mm (SE 2.2) greater if the cow had been treated for a CHDL during life (compared with cows that had not). Additionally, histology demonstrated that new bone development was osteoma, also termed "exostosis." Age explained much of the variation in bone development. The association between bone development and locomotion score during life is a novel finding, and bone development appears specific to CHDL. Bone development on the most severely affected foot was the best explained outcome and would seem most likely to influence locomotion score. To stop irreparable anatomical damage within the foot, early identification of CHDL and effective treatment could be critical.

Developmental bias in the evolution of phalanges.

Evolutionary theory has long argued that the entrenched rules of development constrain the range of variations in a given form, but few empirical examples are known. Here we provide evidence for a very deeply conserved skeletal module constraining the morphology of the phalanges within a digit. We measured the sizes of phalanges within populations of two bird species and found that successive phalanges within a digit exhibit predictable relative proportions, whether those phalanges are nearly equal in size or exhibit a more striking gradient in size from large to small. Experimental perturbations during early stages of digit formation demonstrate that the sizes of the phalanges within a digit are regulated as a system rather than individually. However, the sizes of the phalanges are independent of the metatarsals. Temporal studies indicate that the relative sizes of the phalanges are established at the time of initial cell condensation. Measurements of phalanges across species from six major taxonomic lineages showed that the same predictable range of variants is conserved across vast taxonomic diversity and evolutionary time, starting with the very origins of tetrapods. Although in general phalangeal variations fall within a range of nearly equal-sized phalanges to those following a steep large-to-small gradient, a novel derived condition of excessive elongation of the distal-most phalanges has evolved convergently in multiple lineages, for example under selection for grasping rather than walking or swimming. Even in the context of this exception, phalangeal variations observed in nature are a small subset of potential morphospace.

Quantitative evaluation of bone development of the distal phalanx of the cow hind limb using computed tomography.

Computed tomography (CT) was performed on 400 claws (200 inner and 200 outer claws) of 100 pairs of bovine hind limbs to investigate the etiological theory that an exacerbating factor for ulceration is exostosis of the tuberculum flexorium within the distal phalanx. A variety of morphological changes of the tuberculum flexorium of bovine hind limb claws was visualized by 3-dimensional CT, and the geometry of these claws suggested a growth pattern of bone development with respect to the assumed daily loading patterns. This growth occurs initially at the abaxial caudal aspect of the distal phalanx and is followed by horizontal progression toward the axial aspect. The length of downward bone development on the solar face of the distal phalanx was 2.73±1.32 mm in the outer claws, significantly greater than in the inner claws (2.38±0.96 mm). Ratios of downward (vertical) bone development to the thickness of the subcutis and the corium (VerBD ratios) did not differ between the outer and inner claws (36.7 vs. 38.3%, respectively). Ratios of horizontal bone development to the axial-to-abaxial line of the tuberculum flexorium (HorBD ratios) were approximately 60% for both outer and inner claws. These quantitative measures regarding horizontal and vertical bone development within the distal phalanx were positively correlated with age and VerBD ratios (r=0.53 and r=0.36 for the inner and outer claws, respectively). Correlations between claw width of the outer claw and length of vertical bone development (r=0.43), the HorBD ratio (r=0.51), and the VerBD ratio (r=0.42) suggested that the relative size difference between the inner and outer claws enhances bone development in the outer claw. Correlation coefficients between VerBD and HorBD ratios (r=0.52 and 0.63 for the inner and outer claws, respectively) suggested that horizontal and vertical bone development occurs as a synchronized process within the tuberculum flexorium. This age-related progress of bone development within the tuberculum flexorium is associated with increased exposure to several exacerbating factors and the laminitic process.

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) and Indian hedgehog regulate digit outgrowth mediated by the phalanx-forming region.

Elongation of the digit rays resulting in the formation of a defined number of phalanges is a process poorly understood in mammals, whereas in the chicken distal mesenchymal bone morphogenetic protein (BMP) signaling in the so-called phalanx-forming region (PFR) or digit crescent (DC) seems to be involved. The human brachydactylies (BDs) are inheritable conditions characterized by variable degrees of digit shortening, thus providing an ideal model to analyze the development and elongation of phalanges. We used a mouse model for BDB1 (Ror2(W749X/W749X)) lacking middle phalanges and show that a signaling center corresponding to the chick PFR exists in the mouse, which is diminished in BDB1 mice. This resulted in a strongly impaired elongation of the digit condensations due to reduced chondrogenic commitment of undifferentiated distal mesenchymal cells. We further show that a similar BMP-based mechanism accounts for digit shortening in a mouse model for the closely related condition BDA1 (Ihh(E95K/E95K)), altogether indicating the functional significance of the PFR in mammals. Genetic interaction experiments as well as pathway analysis in BDB1 mice suggest that Indian hedgehog and WNT/beta-catenin signaling, which we show is inhibited by receptor tyrosine kinase-like orphan receptor 2 (ROR2) in distal limb mesenchyme, are acting upstream of BMP signaling in the PFR.

Growth of severely hypoplastic phalanges and metacarpals in symbrachydactyly: an experimental study in mice.

PURPOSE: Severely hypoplastic phalanges and metacarpals in symbrachydactyly are often associated with a delay or failure of primary ossification evident by radiography at birth. However, little is known about the ossification pattern and further growth of severely hypoplastic bones in symbrachydactyly. To clarify this mechanism, we observed development during ossification of the hypoplastic phalanges in brachypodism mice (which carry functional null mutations of growth differentiation factor 5 and exhibit hypoplastic phalanges) as a model of the bone hypoplasia in symbrachydactyly. METHODS: Forelimbs of wild-type and brachypodism mice from embryonic day 16.5 to 21 days after birth were sectioned. We used radiography to examine the progression of ossification; safranin O fast green-iron hematoxylin staining and in situ hybridization for type II collagen to demonstrate cartilage; the transferase-mediated nick end-labeling assay to identify apoptosis; and tartrate-resistant acid phosphatase staining to demonstrate osteoclastic activity. RESULTS: In brachypodism mice, radiography showed markedly delayed ossification of the proximal phalanges in comparison with wild-type mice. Safranin O staining and type II collagen in situ hybridization showed that the cartilage anlagen of the proximal phalanges were extremely small, with diffuse endochondral ossification throughout, resulting in lack of growth plate and chondroepiphysis formation. Apoptotic cells were present under the perichondrium on the plantar side of the proximal phalanges from day 7 after birth and had spread randomly by day 14. Diffuse osteoclastic activity was evident throughout the proximal phalanges from days 7 to 14 after birth. CONCLUSIONS: These results indicate that severely hypoplastic proximal phalanges in brachypodism mice, although showing an endochondral ossification pattern, lack a growth plate and have no potential for secondary growth. These findings may be relevant to the treatment of symbrachydactyly with severely hypoplastic bones, which are not evident radiographically at birth.

Non-vascularized free toe phalanx transplantation in the treatment of symbrachydactyly and constriction ring syndrome.

Forty-eight patients underwent a total number of 113 non-vascularized free toe phalanx transplantations for congenital short digits between 1975 and 2003, a mean number of 2.3 transplanted phalanges per patient. The mean age at the time of initial surgery was 3.6 years (range 6 months to 21 years). The follow-up time ranged from 4 months to 14 years with a mean of 6 years. Sixty-four phalanges showed radiographically measured growth, 22 phalanges showed signs of resorption, while 27 phalanges showed neither growth nor resorption. Resorption increased with patient age. Three patients developed donor site problems. The optimum timing for initial surgery is as early as possible because of the safer and greater growth potential and less resorption of the transplanted phalanges. Non-vascularized free toe phalanx transplantations offer a simple and safe method of lengthening with a significant improvement of hand function.

Long term follow-up of composite non-vascularized toe phalanx transfers for aphalangia.

The results of 21 non-vascularized toe phalanx transfers in 13 patients were reviewed radiologically with respect to function, physeal patency, growth and donor site morbidity at a mean follow-up of 7.4 (range 2.9-13.6) years. Physeal patency was maintained in 4 of 18 surviving transfers. The length of the transferred phalanx averaged 75% of the contralateral comparable toe phalanx and 44% of the contralateral digit proximal phalanx. Most patients had good or simple use of the hand with active joint motion. There was universal shortening of the donor toe with hypoplasia of the middle and distal phalanges. This review suggests that transfer of a non-vascularized toe phalanx provides a reliable but limited means for increasing length of a digit, stabilizing soft tissue "nubbins" and improving function. Longer follow-up has shown more modest gains in growth than in some previous reports.