Evolution of hindlimb bone dimensions and muscle masses in house mice selectively bred for high voluntary wheel‐running behavior

We have used selective breeding with house mice to study coadaptation of morphology and physiology with the evolution of high daily levels of voluntary exercise. Here, we compared hindlimb bones and muscle masses from the 11th generation of four replicate High Runner (HR) lines of house mice bred for high levels of voluntary wheel running with four non‐selected control (C) lines. Mass, length, diameter, and depth of the femur, tibia‐fibula, and metatarsal bones, as well as masses of gastrocnemius and quadriceps muscles, were compared by analysis of covariance with body mass or body length as the covariate. Mice from HR lines had relatively wider distal femora and deeper proximal tibiae, suggesting larger knee surface areas, and larger femoral heads. Sex differences in bone dimensions were also evident, with males having thicker and shorter hindlimb bones when compared with females. Several interactions between sex, linetype, and/or body mass were observed, and analyses split by sex revealed several cases of sex‐specific responses to selection. A subset of the HR mice in two of the four HR lines expressed the mini‐muscle phenotype, characterized mainly by an ～50% reduction in hindlimb muscle mass, caused by a Mendelian recessive mutation, and known to have been under positive selection in the HR lines. Mini‐muscle individuals had elongated distal elements, lighter and thinner hindlimb bones, altered 3rd trochanter muscle insertion positions, and thicker tibia‐fibula distal widths. Finally, several differences in levels of directional or fluctuating asymmetry in bone dimensions were observed between HR and C, mini‐ and normal‐muscled mice, and the sexes. This study demonstrates that skeletal dimensions and muscle masses can evolve rapidly in response to directional selection on locomotor behavior.     

Tibial dimensions before and during the recovery phase in the osteopetrotic mutant mouse.

Osteopetrosis is a genetic bone disease characterized by excessive bone mass and 'clubbing' of long bones. In the osteopetrotic (op) mouse, remission of the disease begins at 45 days of age. This study attempted to describe changes in the op tibia before and during remission. Osteopetrotic and normal littermates were killed at intervals from 10 to 120 days of age. Left tibiae were processed for transmission electron microscopy. Microradiographs of right tibiae were projected and drawn. Bone dimensions were compared between mutants and controls by ANOVA and bones were viewed in a scanning electron microscope. Differences between mutants and controls were: at all ages mutant tibiae were shorter than those of controls; 10-day distal shafts of mutant tibiae were significantly narrower; 30-day proximal shafts of mutant tibiae were wider, distal shafts were narrower, and there was no bone resorption along the external proximal metaphysis. At 48 days, resorption was seen along the proximal metaphyses of the mutant tibiae and by 60 days, extensive resorption areas were evident. However, proximal shafts of mutant tibiae were still significantly wider than those of controls. These results indicated that before remission there was an unequal deposition of bone on the mutant tibia. After remission, resorption occurred along the external proximal shaft, but was not enough to remove significant amounts of bone from the proximal metaphyses of mutant tibiae by 120 days of age.     

Oxygen isotope variability in bones of wild caught and constant temperature reared sub-adult American alligators

(1) The mean delta18O(BP) ( per thousandSMOW) for any given bone sampled from captive alligators maintained at high constant temperature was lower (indicative of higher temperatures of bone deposition) than that of the same bone from wild alligators caught in Northern Florida, but these differences were only greater than two standard deviations from the mean for the thoracic vertebrae and metatarsal bones. (2) Inter-bone variability of delta18O(BP) ( per thousandSMOW) was similar for captive alligators maintained at constant temperatures and the wild alligators, but intra-bone variability was much greater in wild alligators. (3) The order of mean delta18O(BP) ( per thousandSMOW) of bones (from highest to lowest) differed between treatment groups. However, intra-bone variability obscured the significance of those differences. Nevertheless, the thoracic vertebra had the highest mean delta18O(BP) ( per thousandSMOW), indicative of lower temperatures, and the lowest variability of bones in both groups of alligators. Conversely, the tibia was one of the warmest and more variable bones in both groups of alligators. (4) The pattern of delta18O(BP) ( per thousandSMOW) values across sites within long bones were identical between alligator treatment groups for the femur and humerus but differed between groups for the tibia and metatarsus, and differed between different long bones. The predicted intra-bone pattern for long bones of increasing delta18O(BP) ( per thousandSMOW) indicative of lower temperatures in more distal sampling sites was only obtained from the femurs. (5) Paired cortical and cancellous bone samples from the same site from all individuals in both treatment groups were available for proximal humeri and distal femurs. delta18O(BP) ( per thousandSMOW) values from cortical bone were more variable than those from cancellous bone for both bones. (6) Cortical bone had lower delta18O(BP) ( per thousandSMOW) values indicative of warmer temperatures than cancellous bone at sites sampled on the proximal humeri and distal femurs of all three animals from both treatment groups.     

Secular change in long bone length and proportion in the United States, 1800-1970.

We examine secular change in long bone lengths and allometry of Americans dating from the mid-19th century to the 1970s. Skeletal samples were derived from the Huntington Collection, Terry Collection, World War II casualties, and the Forensic Anthropology Data Bank. Regression of bone length on year of birth allowed evaluation of the secular change in bone length. Size was computed as the geometric mean of all bone lengths, and shape as the ratio of each bone to size. These variables were then regressed on year of birth, allowing evaluation of allometric secular change. The results revealed a pattern of change that can be summarized as follows: male secular change is stronger than female, lower limb bone secular change is more pronounced than upper limb bone change, and distal bones change more than proximal bones, particularly in the lower limb. In males, white changes are uniformly higher than black but these differences do not rise to the level of statistical significance. Environmental forces, such as nutrition and disease, are the usual causes of secular changes in overall size. This paper shows that long bone proportions also respond to these same environmental factors. Moreover, the changes in body proportion are likely to be due to allometric consequences of growth changes that occur early in life. Am J Phys Anthropol 110:57-67, 1999.     

Avian long bones, flight and bipedalism.

Morphological, geometrical, chemical and mechanical characteristics of avian long bones are reviewed. Important differences exist between long bones of birds and mammals. Differences are also present in appendicular bones of birds, either between wing bones and leg bones or proximal (stylopodial) long bones and distal (zeugopodial) long bones. Special emphasis is put on pneumatization, in terms of both phylogenetic origin and geometrical and mechanical characteristics linked to it. Cortical thickness, bending strength and flexural Young's modulus were significantly lower in pneumatized bones than in marrow-filled bones. Possible adaptive reasons for the differences shown are discussed.     

Does the occurrence of Harris lines affect the morphology of human long bones?

The purpose of the study is to check the relationship between the occurrence of Harris lines and the morphological differentiation of the long bones of the human skeleton as an indicator of living conditions. The bone material (233 adult individuals, including 120 males and 113 females) was collected at a mediaeval burial ground in Cedynia, Poland. Recommended methods were applied to estimate the sex and age of the individuals (Ferembach et al 1979; Buikstra & Ubelaker 1994). The results obtained indicate that there is no clear relationship between metric characteristics of the studied long bones and the occurrence of Harris lines. Adverse environmental factors, which triggered the occurrence of Harris lines did not strongly affect the growth of long bones and did not change their morphology. Regardless of the phase of ontogenetic development in which the arrested growth lines (HL) formed, no effect of this fact on the final length of bones was observed. Similarly, no statistically significant differences were found in the proportions of bones between individuals reacting to adverse living conditions with the formation of Harris lines and those, whose bones were free of Harris lines. One may assume that Harris lines are of significance in epidemiological research and when assessing the general health profile of a population, but they are less useful in research on morphological reactions of individuals to living conditions.     

四川自贡大山铺中侏罗世蜀龙和峨眉龙长骨骨组织结构的初步研究

通过对四川自贡大山铺恐龙动物群中两种主要蜥脚类恐龙—李氏蜀龙和天府峨眉龙肱骨和尺骨的骨组织结构观察,并与我国晚白垩世的几种恐龙长骨进行对比,结果发现:1)恐龙的长骨都具有快速的后生生长速率;2)恐龙的生长方式属于非限定生长,即在成年后并不停止生长;3)不同类型的恐龙到了成年以后,其骨沉积速率可能有较大差异;4)不同类型的恐龙在长骨的生长改建过程中,骨组织内部的重吸收作用有较大差异;5)生长轮结构在不同部位的骨骼中或在骨骼的生长发育过程中可能也有较大差异。     

Natural markers in bone growth

Three features in the long bones, shown by radiograms, have been used as markers for the study of bone growth.

• (I) Transverse lines of arrested growth. Radiograms of six long limb bones from 1,576 individuals were investigated for clearness and persistence of these lines. Both ends of tibia and fibula showed very high frequency of suitable lines for markers, possibly also the distal end of femur and radius.
• (II) Notches in the base of second and fifth metacarpal bones. Measurements of growth from apex of the basal notch to the ends of the shaft were performed on serial hand radiograms. The proportion of growth from distal and basal ends averaged 87:13 in the second and 80:20 in the fifth metacarpal bones.
• (III) Nutrient canals. The initial point of ossification was determined by a prolongation of the nutrient canal intersecting the central axis of the medullary cavity. The proportion of growth from that point to distal and basal ends of the shaft averaged 68:32 and 64:36 for the second and the fifth metacarpal bones, respectively. These values are significantly different from the measurements obtained from the notches.

     

Regional distribution of mineral and matrix in the femurs of rats flown on Cosmos 1887 biosatellite

We combined biochemical measurements with novel techniques for image analysis in the rat femur to characterize the location and nature of the defect in mineralization known to occur in growing animals after spaceflight. Concentrations of mineral and osteocalcin were low in the distal half of the diaphysis and concentrations of collagen were low with evidence of increased synthesis in the proximal half of the diaphysis of the flight bones. X-ray microtomography provided semiquantitative data in computer-generated sections of whole wet bone that indicated a longitudinal gradient of decreasing mineralization toward the distal diaphysis, similar to the chemistry results. Analysis of embedded sections by backscattered electrons in a scanning electron microscope revealed distinct patterns of mineral distribution in the proximal, central, and distal regions of the diaphysis and also showed a net reduction in mineral levels toward the distal shaft. Increases in mineral density to higher fractions in controls were less in the flight bones at all three levels, with the most distal cross-sectional area most affected. The combined results from these novel techniques identified the areas of femoral diaphysis most vulnerable to the mineralization defect associated with spaceflight and/or the stress of landing.     

Bone adaptation to altered loading after spinal cord injury: a study of bone and muscle strength

Bone loss from the paralysed limbs after spinal cord injury (SCI) is well documented. Under physiological conditions, bones are adapted to forces which mainly emerge from muscle pull. After spinal cord injury (SCI), muscles can no longer contract voluntarily and are merely activated during spasms. Based on the Ashworth scale, previous research has suggested that these spasms may mitigate bone losses. We therefore wished to assess muscle forces after SCI with a more direct measure and compare it to measures of bone strength. We hypothesized that the bones in SCI patients would be in relation to the loss of muscle forces. Six male patients with SCI 6.4 (SD 4.3) years earlier and 6 age-matched, able-bodied control subjects were investigated. Bone scans from the right knee were obtained by pQCT. The knee extensor muscles were electrically stimulated via the femoral nerve, isometric knee extension torque was measured and patellar tendon force was estimated. Tendon force upon electrical stimulation in the SCI group was 75% lower than in the control subjects (p<0.01). Volumetric bone mineral density of the patella and of the proximal tibia epiphysis were 50% lower in the SCI group than in the control subjects (p<0.01). Cortical area was lower by 43% in the SCI patients at the proximal tibia metaphysis, and by 33% at the distal femur metaphysis. No group differences were found in volumetric cortical density. Close curvilinear relationships were found between stress and volumetric density for the tibia epiphysis (r(2)=0.90) and for the patella (r(2)=0.91). A weaker correlation with the tendon force was found for the cortical area of the proximal tibia metaphysis (r(2)=0.63), and none for the distal femur metaphysis. These data suggest that, under steady state conditions after SCI, epiphyseal bones are well adapted to the muscular forces. For the metaphysis of the long bones, such an adaptation appears to be less evident. The reason for this remains unclear.     

Developmental basis of limb length in rodents: evidence for multiple divisions of labor in mechanisms of endochondral bone growth

SUMMARY Mammals are remarkably diverse in limb lengths and proportions, but the number and kind of developmental mechanisms that contribute to length differences between limb bones remain largely unknown. Intra- and interspecific differences in bone length could result from variations in the cellular processes of endochondral bone growth, creating differences in rates of chondrocyte proliferation or hypertrophy, variation in the shape and size of chondrocytes, differences in the number of chondrocytes in precursor populations and throughout growth, or a combination of these mechanisms. To address these questions, this study compared cellular mechanisms of endochondral bone growth in cross-sectional ontogenetic series of the appendicular skeleton of two rodent species: the mouse ( Mus musculus ) and Mongolian gerbil ( Meriones unguiculatus ). Results indicate that multiple cellular processes of endochondral bone growth contribute to phenotypic differences in limb bone length. The data also suggest that separate developmental processes contribute to intraspecific length differences in proximal versus distal limb bones, and that these proximo-distal mechanisms are distinct from mechanisms that contribute to interspecific differences in limb bone length related to body size. These developmental "divisions of labor" are hypothesized to be important features of vertebrate limb development that allow (1) morphology in the autopods to evolve independently of the proximal limb skeleton, and (2) adaptive changes in limb proportions related to locomotion to evolve independently of evolutionary changes in body size.     

A dynamic pattern of mechanical stimulation promotes ossification in avian embryonic long bones

We have performed a set of finite element analyses of embryonic chick hindlimb skeletal rudiments at several time points during development, around the time of initial bone formation. Using optical projection tomography, we created anatomically accurate rudiment and muscle morphologies for each stage. The changes in pattern and magnitude of biophysical stimuli (such as stress, strain, hydrostatic pressure and fluid flow) were computed, and were found to transform as bone formation proceeded in the rudiment. For each biophysical stimulus, a single concentration of the stimulus was predicted at the mid-diaphysis some time before initial bone formation begins. Then, several hours before ossification, two concentrations of the stimuli were predicted distal and proximal to the prospective bone collar. Once bone formation had begun, high concentrations of the stimuli were maintained proximal and distal to the bone collar. We propose the hypothesis that patterns of biophysical stimuli resulting from mechanical loading due to muscle contractions initiate and propagate ossification in avian embryonic long bones, whereby a region of the perichondrium experiences a period of time under high cyclic stimulus levels, promoting chondrocyte hypertrophy at the core and prompting bone collar formation some hours later.     

Connective tissue reinforcing structures of the digital tendon sheaths of the human hand

At a greater number of humid preparated human hands, all the ligamentous supports of the digital tendon sheath were exposed and their dimensions were determined. The osteofibrous channels, which contain the long flexor tendons of the digits, were bounded on the one hand by transversely concave shaft areas of the phalanges and the palmar ligaments and on the other side by the fibrous parts of the tendon sheath. From the second to the 5th finger, it has a regular extension of length, which begins proximal at the heads of the metacarpal bones and runs distal to the base of the nail phalanx. In some cases, there is a continuous communication between the digital tendon sheath of the little finger and the carpal synovial sheath. The tendon sheath of the flexor pollicis longus muscle in comparison with it is always in an open communication with the radial synovial sac of the wrist. At the fibrous supports of the digital tendon sheath, one can find constant and inconstant ligamentous structures. Regular shaped ligaments consist of annular fibers (A1 to A5). The proximal complex of fiber supports is a formation of the A1 and A2 ligaments. The band A1 can be divided into 2 ligaments both of roughly equal length, which lay between the head of the metacarpal bone and the base of the proximal phalanx. The strongest fibrous support of the whole digital tendon sheath represents the band A2. It is attached to the midth of the proximal phalanx and increases in strength from proximal to distal. The middle length varies between 6.7 mm at the thumb and 18.7 mm at the middle finger. The distal margin is strengthened by fibrocartilage tissue to be in accordance with the important function as a pulley. The annular band A4 forms the distal supporting complex height above the shaft of the middle phalanx. At the 2nd to the 5th finger it is, with a middle length of 6 to 7 mm, very much shorter than A2 and restrains first of all the tendon of the flexor digitorum profundus muscle. In the area of the interphalangeal joints, we can find the annular bands A3 and A5, which fiber texture is formed variable. Both ligaments are attached on either both sides with the joint capsule and the palmar plate. The other inconstant supports of the digital sheaths are systematically recorded indeed (C1 to C3), but only in exceptional cases they exist of cruciform fibers (Lig. cruciatum).(ABSTRACT TRUNCATED AT 400 WORDS)     

Development and growth of long bones in European water frogs (Amphibia: Anura: Ranidae), with remarks on age determination

Differentiation and development of long bones were studied in European water frogs: Rana lessonae, R. ridibunda, and R. esculenta. The study included premetamorphic larvae (Gosner Stage 40) to frogs that were 5 years old. Femora, metatarsal bones, and proximal phalanges of the hindlimb exhibit the same pattern of periosteal bone differentiation and the same pattern of growth. Longitudinal and radial growth of these bones was studied by examination of the diaphyses and epiphyses, particularly where the edge of periosteal bone is inserted into the epiphysis. The periosteum seems to be responsible for both longitudinal and radial growth. Investigation of the formation, length, and arrangement of lines of arrested growth reveals that the first line is present only in the middle 25-35% of the length of the diaphysis of an adult bone; therefore, only the central portion of the diaphysis should be used for age estimation in skeletochronological studies. Comparison of the shapes and histological structures of epiphyses in the femur, metatarsal bones, and phalanges revealed that epiphyseal cartilages are composed of an inner and outer part. The inner metaphyseal cartilage has distinct zones and plugs the end of the periosteal bone cylinder; its role in longitudinal growth is questioned. The outer epiphyseal cartilage is composed of articular cartilages proper, in addition to lateral articular cartilages. Differences in the symmetry of the lateral articular cartilages of distal epiphyses of the femur and toes may reflect adaptations to different kinds of movements at the knee and in the foot.     

The differential frequency of preservation of early hominid wrist and hand bones

A survey of hominid hand and wrist bones of Plio-Pleistocene fossil hominid sites in Africa was undertaken. There are 101 specimens in total, from 7 sites. Carpals are most rarely preserved, but certain elements such as the capitate tend to be more frequently preserved than others. There is a preservation rate cline from proximal to distal in the hand, proximal elements (metacarpals) being numerically better preserved than the distal elements (proximal, middle and distal phalanges, in that order of preservation). The proportion of complete, or nearly complete hand and wrist bones is greater in the distal than in the proximal elements. There is no statistical difference in the frequency of preservation of left and right sides, or in the frequency of preservation of proximal and distal ends of individual bones, although there is a tendency for proximal ends to occur more frequently than distal ends. The incidence of hand and wrist bones in fossil deposits is low compared with that of other post-cranial skeletal elements (with the exception of foot bones, where the incidence is similar). This could be accounted for by depositional factors, but preparation techniques and differential collection of specimens may play a role.     

The development of the neurons of the glossopharyngeal (IX) and vagal (X) sensory ganglia in chick embryos

The timetable of cell generation, neuronal death and neuron numbers in the fused proximal glossopharyngeal (IX) and vagal (X) ganglion and distal IX and X ganglia were studied in normal and nerve growth factor (NGF) treated chick embryos. 3H-thymidine was injected between the 3rd and 7th days of incubation and embryos sacrificed on the 11th day. Neurons in the distal IX and X ganglia were generated between the 2nd and 5th days of incubation, the peak mitotic activity occurring on the 4th and 3rd days, respectively. Neurons of the proximal IX and X ganglion were generated between the 4th and 7th days, with maximum neuron generation on the 5th day of incubation. Counts of neurons in the 3 ganglia between the 5th and 18th days of incubation showed a maximum of 22,000 on the 8th day in the proximal IX and X ganglion and this decreased to 12,000 by the 13th day. In the distal IX ganglion, the neuron number decreased by 44% from 4,500 on the 6th day to 2,500 by the 11th day. A similar decrease of 43% was found in the distal X ganglion, the neuron number falling from 11,500 on the 7th day to 6,500 by the 11th day of incubation. Neuronal cell death in these ganglia extended from the 5th to the 12th day of incubation, maximum cell death occurring at or after the cessation of mitotic activity. NGF administration from the 5th to the 11th day of incubation did not have a measurable effect on the neurons of proximal IX and X and distal IX ganglia, but increased neuronal survival by 30% in the distal X ganglion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth and shaping of metacarpal and carpal cartilage anlagen: application of morphometry to the development of short and long bone. A study of human hand anlagen in the fetal period

A histological and morphometric analysis of human metacarpal and carpal anlagen between the 16th and 22nd embryonic weeks was carried out with the aim of studying the establishment of the respective anlage architecture. No differences in the pattern of growth were documented between the peripheral and central zones of the metacarpal epiphyses and those of the carpals. The regulation of longitudinal growth in long bone anlagen occurred in the transition zone between the epiphysis and the diaphysis (homologous to the metaphyseal growth plate cartilage in more advanced developmental stage of the bone). Comparative zonal analysis was conducted to assess the chondrocyte density, the mean chondrocyte lacunar area, the paired chondrocyte polarity in the orthogonal longitudinal and transverse planes, and the lacunar shape transformation in the metacarpal. In transition from epiphysis to diaphysis chondrocyte density decreased and mean lacunar area increased. No significant differences in the chondrocyte maturation cycle were observed between proximal/distal metacarpal epiphyses and the carpal anlagen. The number of paired chondrocyte oriented along the growth vector was significantly higher in both proximal/distal transition zones between epiphysis and diaphysis. Human metacarpals shared with experimental models (like mice and nonmammal tetrapods) an early common chondrocyte maturation cycle but with a different timing due to the slower embryonic and fetal developmental rate of human anlagen.     

Development of the innervation of long bones: expression of the growth-associated protein 43

It has been known from clinical and experimental observations that the peripheral nervous system is involved in the development of long bones. Expression of growth-associated protein 43 (GAP-43/B-50) was found in axonal growth cones during embryonic and postnatal ontogeny as well as in regenerating axons after nerve injury. The aim of the present study was to examine the occurrence of growing nerve fibers in rat tibia from gestational day 16 (GD 16) to postnatal day 28 (PD28). An indirect immunoenzymatic reaction using antibodies raised against GAP-43 was applied to detect outgrowing nerve fibers penetrating into the developing bone. On GD 16 and GD 17 no GAP-43-immunoreactive (IR) fibers were observed in the close vicinity of bone rudiments. On GD19 GAP-43-IR fibers were scarcely present within the periosteum of the central portion of the diaphysis. In the perichondrium surrounding the proximal epiphysis, nerve fibers were first detected around birth. From PD1 onward, numerous fibers were seen in the fibrous buds of the perichondrium at the epi-metaphyseal junction (Ranvier's grooves), some of them being adjacent to the blood vessels. Nerve fibers penetrating into the bone and located in the bone marrow, predominantly associated with blood vessels, were first observed on GD21 and their number increased with further development. They were initially located in the central portion of the diaphysis and later extended towards the metaphyses. On PD4 an increased number of GAP-43-IR fibers appeared in the perichondrium of proximal and distal epiphyses. In the fibrous strands penetrating into the epiphyses and in the secondary ossification centers, nerve fibers were first observed on PD10. From PD14 onward the pattern of tibial innervation remained unchanged but the intensity of GAP-43 immunostaining visibly decreased. The present study demonstrates that developing long bones of rat hindlimbs are supplied by growing nerve fibers immunoreactive for GAP-43 from GD 19 onward. Time and location of their appearance were at least partially correlated with known events taking place during long bone development, e.g. formation of primary and secondary ossification centers. Decreased expression of GAP-43 immunoreactivity in later developmental stages is believed to reflect nerve fiber maturation.     

Incidence and mechanical significance of pneumatization in the long bones of birds

The incidence of pneumatization in avian long bones was studied, by direct observation, in a large sample of species. Only proximal bones (humerus and femur) presented pneumatization in the sample studied. The incidence obtained was related to the variation of the maximum cortical thickness and mechanical properties, such as bending strength and flexural Young's modulus. Cortical thickness, bending strength and flexural Young's modulus were significantly lower in pneumatized bones than in marrow-filled bones. Furthermore, some congruence was found between pneumatization and systematic groups when compared. In this sense, Charadriformes was the only order studied with total absence of long bone pneumatization. Results on cortical thickness appear to be in agreement with modelling predictions previously made and with results obtained on other groups of flying vertebrates. The possible selective advantage of reduction in cortical thickness in relation to flying is suggested.     

Isometric Scaling in Developing Long Bones Is Achieved by an Optimal Epiphyseal Growth Balance

One of the major challenges that developing organs face is scaling, that is, the adjustment of physical proportions during the massive increase in size. Although organ scaling is fundamental for development and function, little is known about the mechanisms that regulate it. Bone superstructures are projections that typically serve for tendon and ligament insertion or articulation and, therefore, their position along the bone is crucial for musculoskeletal functionality. As bones are rigid structures that elongate only from their ends, it is unclear how superstructure positions are regulated during growth to end up in the right locations. Here, we document the process of longitudinal scaling in developing mouse long bones and uncover the mechanism that regulates it. To that end, we performed a computational analysis of hundreds of three-dimensional micro-CT images, using a newly developed method for recovering the morphogenetic sequence of developing bones. Strikingly, analysis revealed that the relative position of all superstructures along the bone is highly preserved during more than a 5-fold increase in length, indicating isometric scaling. It has been suggested that during development, bone superstructures are continuously reconstructed and relocated along the shaft, a process known as drift. Surprisingly, our results showed that most superstructures did not drift at all. Instead, we identified a novel mechanism for bone scaling, whereby each bone exhibits a specific and unique balance between proximal and distal growth rates, which accurately maintains the relative position of its superstructures. Moreover, we show mathematically that this mechanism minimizes the cumulative drift of all superstructures, thereby optimizing the scaling process. Our study reveals a general mechanism for the scaling of developing bones. More broadly, these findings suggest an evolutionary mechanism that facilitates variability in bone morphology by controlling the activity of individual epiphyseal plates.