The role of radiography in diagnosing, monitoring and prognosing juvenile idiopathic arthritis.

The current role of conventional radiography in the diagnosis, monitoring and prognosis of juvenile idiopathic arthritis (JIA) is reviewed, as its role has changed with the increasing use of ultrasound and magnetic resonance imaging, as well as with the introduction of biological drugs. Conventional radiography does not play an important role in the diagnosis of JIA, as this is based on history, clinical examination and laboratory findings. The main role of conventional radiography is in the detection and monitoring of growth disorders and chronic structural and morphological changes of the affected joints and bones, in addition to helping with the differential diagnosis of conditions that mimic JIA. Radiographic changes of the joints depend on the age of the child, the type and duration of arthritis and the specific joints affected. There are no standard protocols for arthritis monitoring and most indications for imaging are based on individual case-by-case decisions. The development of degenerative joint changes is considered a poor predictive factor, but there are no clear studies that more precisely define the predictive value of radiographic changes. Conventional radiography remains an important imaging modality in narrowing the differential diagnosis and in evaluating growth disorders and the developing destructive joint changes.

Impact of fluoride and aluminum co-exposure on bone growth and quality in juvenile rats: dose and duration effects.

This study aimed to investigate the impact of the dosage and duration of fluoride and aluminum(F and Al) co-exposure on the skeletal growth and bone quality of juvenile rats. Forty-eight 8-week-old Sprague-Dawley rats were randomly assigned to normal control, low F and Al exposure, and high F and Al exposure groups, with 45-day and 90-day subgroups established for each. We measured body length, tibia length, conducted bone histomorphometric analysis of the proximal tibia, performed micro-CT scans and three-point bending tests of the femur. Compared to the age-matched control group, the low F and Al group at 45 days exhibited increased bone formation and stiffness; the low F and Al group at 90 days and the high F and Al group at 45 days showed increases in body length, tibia length, growth plate width, longitudinal bone growth rate, bone turnover, and improved microstructure. Notably, bone elastic stress only elevated in the high F and Al group at 45 days. Conversely, the high F and Al exposure group at 90 days experienced decreases in the aforementioned parameters, with the exception of growth plate width, and displayed abnormal hypertrophic chondrocyte morphology in the growth plate. In summary, long-term exposure to low levels of F and Al and short-term exposure to high levels of F and Al promote bone formation followed by bone resorption in juvenile rats, stimulating bone growth and enhancing bone quality. However, long-term exposure to high levels F and Al results in low bone turnover, slow bone growth, and reduced bone property.

Maternal F-53B exposure during pregnancy and lactation affects bone growth and development in male offspring.

6:2 Chlorinated polyfluoroalkyl ether sulfonate (F-53B) is a new type of perfluorinated and polyfluoroalkyl substance (PFAS) that is used extensively in industry and manufacturing. F-53B causes damage to multiple mammalian organs. However, the impacts of F-53B on bone are unknown. Maternal exposure to F-53B is of particular concern because of the vulnerability of the developing fetus and newborn to contaminants from the mother. The goal of this study was to examine the impacts of maternal F-53B exposure on bone growth and development in offspring and to explore its underlying mechanisms. Herein, C57BL/6 J mice were given free access to deionized water containing 0, 0.57, or 5.7 mg/L F-53B during pregnancy and lactation. F-53B exposure resulted in impaired liver function, decreased IGF-1 secretion, dysregulation of bone metabolism and disruption of the dynamic balance between osteoblasts and osteoclasts in male offspring. F-53B inhibits longitudinal bone growth and development and causes osteoporosis in male offspring. F-53B may affect the growth and development of offspring bone via the IGF-1/OPG/RANKL/CTSK signaling pathway. This study provides new insights for the study of short stature and bone injury caused by F-53B.

The true history of the Hueter-Volkmann law.

INTRODUCTION: The Hueter-Volkmann law (HVL) of the response of growth plate to compression load is a basic concept in orthopaedics. However, little is known about the origin of HVL and its history. MATERIALS AND METHODS: A literature search was performed in original publications and historical sources. RESULTS: An analysis of all Volkmann´s and Hueter´s texts has shown that none of their publications was based on experiments, but on the data in the literature and their own clinical observations. They did not deal at all with the effect of pressure on the growth plate and mentioned this structure only marginally. The authors coined the opinion that increased pressure retards and decreased pressure accelerates bone growth. Julius Wolff criticized the HVL and concentrated all his arguments in the book "The law of bone remodeling". According to him, increased pressure leads to bone formation, decreased pressure to its resorption. The Wolff-Volkmann dispute was addressed in the German literature by a number of authors. Walther Müller in his monograph "The normal and pathological physiology of the bone" criticized Wolff for his concept of interstitial bone growth. In Müller´s view, HVL applies to the growing bone and Wolff confuses growth with hypertrophy of the mature bone. CONCLUSION: The circumstances of the emergence of HVL are inaccurately and incompletely described in the current literature, as they are mostly taken from secondary sources. HVL, as it is presented today, is not the original formulation, but the result of a long historical evolution.

Early history of the study of bone growth (1722-1875).

INTRODUCTION: Bone growth is a fascinating process, primarily due to its complexity. Equally engaging is the history of its study, which, however, remains unknown to most anatomists and surgeons. MATERIALS AND METHODS: A literature search was performed in original publications and historical sources. RESULTS: The early history of bone growth study may be divided into two periods. Firstly, the experimental one, between 1722 and 1847, which consisted in the study of bone growth by the drilling of benchmark holes into the diaphysis, and examination of growing bones in madder-fed animals. In the course of one century, four French scientists (Henri-Louis Duhamel du Monceau, Marie-Jean-Pierre Flourens, Gaspard Auguste Brullé and Frédéric Léopold Hugueny) and one British researcher (John Hunter) proved experimentally that the longitudinal growth of long bones occurred only at its epiphyseal ends and their final shape resulted from apposition and resorption processes taking place simultaneously both on the periosteal and intramedullary surfaces of the bone. In the second, the microscopic period (1836-1875), the physeal growth cartilage was discovered and described in detail, including its importance for the longitudinal growth of long bones. The first description of growth cartilage was published by a Swiss anatomist Miescher in 1836. Subsequently, this structure was studied by a number of English, German and French anatomists and surgeons. This whole period was concluded by Alfred Kölliker´s extensive study of bone resorption and its significance for typical bone shapes and Karl Langer´s study of the vascular supply of the growing and mature bone. CONCLUSION: Research by French, English, German and Swiss scientists between 1727 and 1875 yielded fundamental insights into the growth of long bones, most of which are still valid today.

A novel pulsed electromagnetic field device as an adjunct therapy to surgical treatment of distal radius fractures: a prospective, double-blind, sham-controlled, randomized pilot study.

INTRODUCTION: The purpose of this study is to evaluate whether using a Fracture Healing Patch (FHP) device that generates pulsed electromagnetic fields (PEMF), applied at the fracture site immediately after open reduction and internal fixation surgery, can accelerate healing of acute distal radius fractures. METHODS: In a prospective, double-blind, randomized, and sham-controlled study, thirty-two patients with DRFs treated with ORIF were included. Patients were allocated to a PEMF (active) group (n = 15) or a control (sham) group (n = 17). All patients were assessed with regard to functional Patient-Rated Wrist Evaluation (PRWE), SF12, and radiological union outcomes (X-rays and computed tomography (CT) scans) at 2, 4, 6, and 12 weeks postoperatively. RESULTS: Patients treated with the FHP demonstrated significantly bone bridging at 4 weeks as assessed by CT (70% vs 54%, p = 0.05). Mean grip strength in the active group was significantly higher as compared to control (16 ± 9 kg vs 7 ± 3.5 kg, respectively, p = 0. 02). The function subscale of the PRWE was significantly better in PEMF-treated group at 6 weeks after surgery (27.2 VS 35.5, p = 0.04). No statistically significant differences were found in SF12. CONCLUSION: PEMF application after ORIF of DRFs is safe, may accelerate bone healing which could lead to an earlier return to daily life activities and work. LEVEL OF EVIDENCE: I.

Plasma exosome miRNA-26b-3p derived from idiopathic short stature impairs longitudinal bone growth via the AKAP2/ERK1/2 axis.

BACKGROUND: Currently, the etiology of idiopathic short stature (ISS) is still unclear. The poor understanding of the molecular mechanisms of ISS has largely restricted this strategy towards safe and effective clinical therapies. METHODS: The plasma exosomes of ISS children were co-cultured with normal human chondrocytes. The differential expression of exosome miRNA between ISS and normal children was identified via high-throughput microRNA sequencing and bioinformatics analysis. Immunohistochemistry, In situ hybridization, RT-qPCR, western blotting, luciferase expression, and gene overexpression and knockdown were performed to reveal the key signaling pathways that exosome miRNA of aberrant expression in ISS children impairs longitudinal bone growth. RESULTS: Chondrocytes proliferation and endochondral ossification were suppressed after coculture of ISS plasma exosomes with human normal chondrocytes. High-throughput microRNA sequencing and RT-qPCR confirmed that plasma exosome miR-26b-3p was upregulated in ISS children. Meanwhile, exosome miRNA-26b-3p showed a high specificity and sensitivity in discriminating ISS from normal children. The rescue experiment showed that downregulation of miR-26b-3p obviously improved the repression of chondrocyte proliferation and endochondral ossification caused by ISS exosomes. Subsequently, miR-26b-3p overexpression inhibited chondrocyte proliferation and endochondral ossification once again. In situ hybridization confirmed the colocalization of miR-26b-3p with AKAP2 in chondrocytes. In vitro and in vivo assay revealed exosome miRNA-26b-3p impairs longitudinal bone growth via the AKAP2 /ERK1/2 axis. CONCLUSIONS: This study is the first to confirm that miR-26b-3p overexpression in ISS plasma exosomes leads to disorders in proliferation and endochondral ossification of growth plate cartilage via inhibition of AKAP2/ERK1/2 axis, thereby inducing ISS. This study provides a new research direction for the etiology and pathology of ISS and a new idea for the biological treatment of ISS.

Proteomic Identification of Plasma Components in Tachypleus tridentatus and Their Effects on the Longitudinal Bone Growth Rate in Rats.

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10-30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10-30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10-30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent.

The Effects of Natural Product-Derived Extracts for Longitudinal Bone Growth: An Overview of In Vivo Experiments.

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children's height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies.

Telomerase expression marks transitional growth-associated skeletal progenitor/stem cells.

Skeletal progenitor/stem cells (SSCs) play a critical role in postnatal bone growth and maintenance. Telomerase (Tert) activity prevents cellular senescence and is required for maintenance of stem cells in self-renewing tissues. Here we investigated the role of mTert-expressing cells in postnatal mouse long bone and found that mTert expression is enriched at the time of adolescent bone growth. mTert-GFP+ cells were identified in regions known to house SSCs, including the metaphyseal stroma, growth plate, and the bone marrow. We also show that mTert-expressing cells are a distinct SSC population with enriched colony-forming capacity and contribute to multiple mesenchymal lineages, in vitro. In contrast, in vivo lineage-tracing studies identified mTert+ cells as osteochondral progenitors and contribute to the bone-forming cell pool during endochondral bone growth with a subset persisting into adulthood. Taken together, our results show that mTert expression is temporally regulated and marks SSCs during a discrete phase of transitional growth between rapid bone growth and maintenance.

Cortical bone development, maintenance and porosity: genetic alterations in humans and mice influencing chondrocytes, osteoclasts, osteoblasts and osteocytes.

Cortical bone structure is a crucial determinant of bone strength, yet for many years studies of novel genes and cell signalling pathways regulating bone strength have focused on the control of trabecular bone mass. Here we focus on mechanisms responsible for cortical bone development, growth, and degeneration, and describe some recently described genetic-driven modifications in humans and mice that reveal how these processes may be controlled. We start with embryonic osteogenesis of preliminary bone structures preceding the cortex and describe how this structure consolidates then matures to a dense, vascularised cortex containing an increasing proportion of lamellar bone. These processes include modelling-induced, and load-dependent, asymmetric cortical expansion, which enables the cortex's transition from a highly porous woven structure to a consolidated and thickened highly mineralised lamellar bone structure, infiltrated by vascular channels. Sex-specific differences emerge during this process. With aging, the process of consolidation reverses: cortical pores enlarge, leading to greater cortical porosity, trabecularisation and loss of bone strength. Each process requires co-ordination between bone formation, bone mineralisation, vascularisation, and bone resorption, with a need for locational-, spatial- and cell-specific signalling pathways to mediate this co-ordination. We will discuss these processes, and a number of cell-signalling pathways identified in both murine and human genetic studies to regulate cortical bone mass, including signalling through gp130, STAT3, PTHR1, WNT16, NOTCH, NOTUM and sFRP4.

Mechanisms by which sialylated milk oligosaccharides impact bone biology in a gnotobiotic mouse model of infant undernutrition.

Undernutrition in children is a pressing global health problem, manifested in part by impaired linear growth (stunting). Current nutritional interventions have been largely ineffective in overcoming stunting, emphasizing the need to obtain better understanding of its underlying causes. Treating Bangladeshi children with severe acute malnutrition with therapeutic foods reduced plasma levels of a biomarker of osteoclastic activity without affecting biomarkers of osteoblastic activity or improving their severe stunting. To characterize interactions among the gut microbiota, human milk oligosaccharides (HMOs), and osteoclast and osteoblast biology, young germ-free mice were colonized with cultured bacterial strains from a 6-mo-old stunted infant and fed a diet mimicking that consumed by the donor population. Adding purified bovine sialylated milk oligosaccharides (S-BMO) with structures similar to those in human milk to this diet increased femoral trabecular bone volume and cortical thickness, reduced osteoclasts and their bone marrow progenitors, and altered regulators of osteoclastogenesis and mediators of Th2 responses. Comparisons of germ-free and colonized mice revealed S-BMO-dependent and microbiota-dependent increases in cecal levels of succinate, increased numbers of small intestinal tuft cells, and evidence for activation of a succinate-induced tuft cell signaling pathway linked to Th2 immune responses. A prominent fucosylated HMO, 2'-fucosyllactose, failed to elicit these changes in bone biology, highlighting the structural specificity of the S-BMO effects. These results underscore the need to further characterize the balance between, and determinants of, osteoclastic and osteoblastic activity in stunted infants/children, and suggest that certain milk oligosaccharides may have therapeutic utility in this setting.

Autogenous bone-guided induced membrane technique in closed/small-sized open high-energy fractures in benign inflammatory environment: a case series.

OBJECTIVE: Infection and nonunion are the two most challenging issues for high-energy fractures. This study aimed to explore the clinical effect of benign inflammation-cultivated bone growth activity in the treatment of closed/small-sized open and high-energy fractures. METHODS: This study is a case series of closed/small-sized open and high-energy fractures of the lower limbs treated at our hospital from April 2009 to February 2017. All patients underwent debridement and external fixation in the early stage, followed by internal fixation in the second stage. After the operation, fracture healing was monitored by X-ray, and early-stage knee function training was initiated. Also, bone grafting was performed to stimulate the healing reaction, eliminating the atrophic nonunion factors. RESULTS: The operation in all 75 cases was carried out after the inflammatory responses completely subsided, leading to secondary wound healing. Bony union appeared in 71 patients who did not suffer from any pain and could stand up and walk without any restriction. Among them, 68 patients could flex their knee > 100°, and three patients had knee flexion ranging from 80 to 100°. No infections occurred after the second operation. CONCLUSION: This two-stage treatment for high-energy fractures could avoid the damage caused by excessive inflammatory responses that occurred following early-stage one-time internal fixation. This method protected benign inflammatory-callus reactions induced by the primary injury and utilized the advantages of closed reduction in AO fixation with open reduction, thereby avoiding potential infection and nonunion caused by one-time fixation during the early stage.

Molecular Mechanism of Induction of Bone Growth by the C-Type Natriuretic Peptide.

The skeletal development process in the body occurs through sequential cellular and molecular processes called endochondral ossification. Endochondral ossification occurs in the growth plate where chondrocytes differentiate from resting, proliferative, hypertrophic to calcified zones. Natriuretic peptides (NPTs) are peptide hormones with multiple functions, including regulation of blood pressure, water-mineral balance, and many metabolic processes. NPTs secreted from the heart activate different tissues and organs, working in a paracrine or autocrine manner. One of the natriuretic peptides, C-type natriuretic peptide-, induces bone growth through several mechanisms. This review will summarize the knowledge, including the newest discoveries, of the mechanism of CNP activation in bone growth.

Probiotics Enhance Bone Growth and Rescue BMP Inhibition: New Transgenic Zebrafish Lines to Study Bone Health.

Zebrafish larvae, especially gene-specific mutants and transgenic lines, are increasingly used to study vertebrate skeletal development and human pathologies such as osteoporosis, osteopetrosis and osteoarthritis. Probiotics have been recognized in recent years as a prophylactic treatment for various bone health issues in humans. Here, we present two new zebrafish transgenic lines containing the coding sequences for fluorescent proteins inserted into the endogenous genes for sp7 and col10a1a with larvae displaying fluorescence in developing osteoblasts and the bone extracellular matrix (mineralized or non-mineralized), respectively. Furthermore, we use these transgenic lines to show that exposure to two different probiotics, Bacillus subtilis and Lactococcus lactis, leads to an increase in osteoblast formation and bone matrix growth and mineralization. Gene expression analysis revealed the effect of the probiotics, particularly Bacillus subtilis, in modulating several skeletal development genes, such as runx2, sp7, spp1 and col10a1a, further supporting their ability to improve bone health. Bacillus subtilis was the more potent probiotic able to significantly reverse the inhibition of bone matrix formation when larvae were exposed to a BMP inhibitor (LDN212854).

A novel technique for prevention of anterior fistula and facilitation of alveolar cleft repair: Gingivoperiosteoplasty with palatoplasty.

Background & Objectives: The Cleft palate is one of the most commonly encountered congenital deformity in plastic surgery clinics and can be associated with cleft lip and alveolus. Though palate repair can be associated with several complications, the most frequent and troublesome is anterior fistula formation. Various technical modifications are in practice to avoid this dreaded complication. We have started combining gingivoperiosteoplasty with palate repair to avoid postoperative anterior fistula formation and to close alveolar cleft at the same time. Methods: A prospective study was performed at the department of plastic and reconstructive surgery, Liaquat National Hospital, Karachi and selected patients were enrolled in the study after informed consent. A total of 15 patients were operated on from January 2017 to December 2020. All patients had cleft palate repair along with primary gingivoperiosteoplasty (GPP) at the age of standard palatal repair. Buccal/oral and nasal layers of the alveolus were dissected as per standard gingivoperiosteoplasty and repaired in continuation with nasal and oral layers of the palate. Postoperatively, the standard cleft palate repair protocol was followed. Follow-up was done at four weeks, 12 weeks, and six months and repair integrity was checked. Future follow-up at 4-5 years of age is planned to see the effect on alveolar collapse, bone growth, and the need for secondary bone grafting. Results: All patients were followed up regularly. None had a complication of fistula. The repairs of both palate and alveolus remained intact. Patients were kept on the follow-up to assess the need for alveolar bone grafting in the future. Conclusion: Gingivoperiosteoplasty combined with the palatal repair is a novel technique for the prevention of anterior palatal fistula.

[Paramedical care related to the implantation of a motorized spinal lengthening nail]. / Soins paramédicaux liés à l'implantation d'un clou d'allongement médullaire motorisé.

The Fitbone® system is one of the most recent motorized bone lengthening techniques. It allows a precise control of the extension while reducing pain and complications. It requires special assistance from the paramedical team, before and after the procedure, as it may cause adjustment problems in some patients.

[Podiatric care of inequality of the lower limbs]. / La prise en soins podologiques de l'inégalité des membres inférieurs.

The podiatrist plays a central role in the treatment of leg length inequality. He remains a privileged interlocutor of parents and children in full development whom he meets at each growth spurt, and therefore at each change of material proposed. His goal is to compensate for the missing centimeters while waiting for surgery in order to avoid unsightly lameness, unilateral equinus of the foot and disharmony of the upper floors. Solutions range from foot orthoses to orthopedic shoes.

[Social management of patients affected by a bone growth problem]. / Prise en charge sociale des patients touchés par un problème de croissance osseuse.

Children and adolescents with a bone growth disorder need lifelong medical care. The establishment of a social support system allows them to benefit from the necessary assistance for the evolution of their pathology, from birth to their entry into school and then into professional life.

Long bone histomorphogenesis of the naked mole-rat: Histodiversity and intraspecific variation.

Lacking fur, living in eusocial colonies and having the longest lifespan of any rodent, makes naked mole-rats (NMRs) rather peculiar mammals. Although they exhibit a high degree of polymorphism, skeletal plasticity and are considered a novel model to assess the effects of delayed puberty on the skeletal system, scarce information on their morphogenesis exists. Here, we examined a large ontogenetic sample (n = 76) of subordinate individuals to assess the pattern of bone growth and bone microstructure of fore- and hindlimb bones by using histomorphological techniques. Over 290 undecalcified thin cross-sections from the midshaft of the humerus, ulna, femur, and tibia from pups, juveniles and adults were analyzed with polarized light microscopy. Similar to other fossorial mammals, NMRs exhibited a systematic cortical thickening of their long bones, which clearly indicates a conserved functional adaptation to withstand the mechanical strains imposed during digging, regardless of their chisel-tooth predominance. We describe a high histodiversity of bone matrices and the formation of secondary osteons in NMRs. The bones of pups are extremely thin-walled and grow by periosteal bone formation coupled with considerable expansion of the medullary cavity, a process probably tightly regulated and adapted to optimize the amount of minerals destined for skeletal development, to thus allow the female breeder to produce a higher number of pups, as well as several litters. Subsequent cortical thickening in juveniles involves high amounts of endosteal bone apposition, which contrasts with the bone modeling of other mammals where a periosteal predominance exists. Adults have bone matrices predominantly consisting of parallel-fibered bone and lamellar bone, which indicate intermediate to slow rates of osteogenesis, as well as the development of poorly vascularized lamellar-zonal tissues separated by lines of arrested growth (LAGs) and annuli. These features reflect the low metabolism, low body temperature and slow growth rates reported for this species, as well as indicate a cyclical pattern of osteogenesis. The presence of LAGs in captive individuals was striking and indicates that postnatal osteogenesis and its consequent cortical stratification most likely represents a plesiomorphic thermometabolic strategy among endotherms which has been suggested to be regulated by endogenous rhythms. However, the generalized presence of LAGs in this and other subterranean taxa in the wild, as well as recent investigations on variability of environmental conditions in burrow systems, supports the hypothesis that underground environments experience seasonal fluctuations that may influence the postnatal osteogenesis of animals by limiting the extension of burrow systems during the unfavorable dry seasons and therefore the finding of food resources. Additionally, the intraspecific variation found in the formation of bone tissue matrices and vascularization suggested a high degree of developmental plasticity in NMRs, which may help explaining the polymorphism reported for this species. The results obtained here represent a valuable contribution to understanding the relationship of several aspects involved in the morphogenesis of the skeletal system of a mammal with extraordinary adaptations.