Talk:Musculoskeletal System - Bone Development Timeline

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Cite this page: Hill, M.A. (2019, September 17) Embryology Musculoskeletal System - Bone Development Timeline. Retrieved from


CT evaluation of timing for ossification of the medial clavicular epiphysis in a contemporary Western Australian population

Int J Legal Med. 2014 Nov 15. [Epub ahead of print]

Franklin D1, Flavel A.


The clavicle is the first bone to ossify in the developing embryo and the last to complete epiphyseal union. It is the latter sustained period of growth that has attracted the interest of skeletal biologists and forensic practitioners alike, who collectively recognize the important opportunity this bone affords to estimate skeletal age across the prenatal to early adult lifespan. Current research is largely directed towards evaluating the applicability of assessing fusion in the medial epiphysis, specifically for determining age of majority in the living. This study aims to contribute further insights, and inform medicolegal practice, by evaluating the Schmeling five-stage system for the assessment of clavicular development in a Western Australian population. We retrospectively evaluated high-resolution multiple detector computed tomography (MDCT) scans of 388 individuals (210 male; 178 female) between 10 and 35 years of age. Scans are viewed in axial and multiplanar reconstructed (MPR) images using OsiriX®. Fusion status is scored according to a five-stage system. Transition analysis is used to calculate age ranges and determine the mean age for transition between an unfused, fusing and fused status. The maximum likelihood estimates (in years) for transition from unfused to fusing is 20.60 (male) and 19.19 (female); transition from fusing to complete fusion is 21.92 (male) and 21.47 (female). Results of the present study confirm the reliability of the assessed method and demonstrate remarkable consistency to data reported for other global populations.

PMID 25398635


Ossification of the vertebral column in human foetuses: histological and computed tomography studies

Folia Morphol (Warsz). 2013 Aug;72(3):230-8.

Skórzewska A, Grzymisławska M, Bruska M, Lupicka J, Woźniak W. Author information


There is no agreement in the literature as to the time of the onset and progress of the vertebral column ossification. The aim of the present study was to determine the precise sequence of ossification of the neural arches and vertebral centra.Histological and radiographic studies were performed on 27 human foetuses aged from 9 to 21 weeks. It was found that the ossification of vertebrae commences in foetuses aged 10 and 11 weeks. Ossification centres appear first for neuralarches in the cervical and upper thoracic vertebrae and by the end of 11th week they are present in all thoracic and lumbar neural arches. In the vertebral centrain foetus of 10 weeks ossification was found in the lower 7 thoracic and first lumbar vertebrae. By the end of 11th week ossification is present in the lower 4 cervical, all thoracic, all lumbar and 4 sacral vertebral centra. The study indicates that ossification of the neural arches proceeds in the craniocaudal direction,whereas in the vertebral centra it progresses from the lower thoracic vertebrae into both directions. Different shapes of ossification centres were also described.

PMID 24068685

Development of human hip joint in the second and the third trimester of pregnancy; a cadaveric study

BMC Dev Biol. 2013 May 7;13:19. doi: 10.1186/1471-213X-13-19.

Masłoń A, Sibiński M, Topol M, Krajewski K, Grzegorzewski A. Source Clinic of Orthopaedics and Paediatric Orthopaedics, Medical University of Lodz, Lodz, Poland. Abstract BACKGROUND: The purpose of the study was an evaluation of fetal hip joint morphology during the second and the third trimester of pregnancy. Serial sections were performed on 23 cadaver infants. RESULTS: The mean lunar age was 6.6 months. Femoral shaft length (FSL) and width of the proximal and distal epiphysis were x-rayed to determine fetal age. The neck shaft angle (NSA), the femoral antetorsion angle (FAA), the acetabulum anteversion angle (AAA) and the acetabulum slope angle (ASA) were measured. Hip development ratios were plotted for all cadaveric species and revealed: flat FSL/NSA slope pattern, upward FSL/FAA slope pattern and downward slope pattern for FSL/ASA and FSL/AAA ratios. The changes, observed during the developmental period, were not statistically significant. NSA did not change during the second or the third pregnancy trimester. FAA increased during pregnancy but the changes were not statistically significant. AA, as well as ASA, showed a decreasing trend during the second and the third pregnancy trimester, however, with no correlations to age. CONCLUSION: Despite an increasing depth and growing dimensions of the acetabulum in the uterus, its orientation does not change in any significant way.

PMID 23651510


Anatomy and development of the craniovertebral junction

Neurol Sci. 2011 Dec;32 Suppl 3:267-70.

Raybaud C. Source Department of Neuroradiology, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G1X8, Canada, Abstract The occipital bone is the upper end of the somatic spine, limited cranially by the tentorium. The bony craniovertebral junction (caudal occiput, atlas, and axis) is interposed between the unsegmented occipital and the intersegmental spinal sclerotomes, separated from the occiput and C3 by the intrasegmental clefts of O4 and C2 sclerotomes, respectively. It retains a primitive segmental hypocentrum (anterior arch of C1) and is unsegmented from caudal O4 to cranial C2 half-sclerotomes (axis). Its morphology relates to the dual function of providing support and mobility (visual/olfactory/auditory pursuit, oral prehension) to the head. The early notochord passes through the odontoid tip to the basiocciput surface before entering the clivus up to the craniopharyngeal canal; later, the rostralmost chordal remnant is the C2/3 nucleus pulposus. Chondrification starts in the second fetal month and ossification in the fetal or postnatal periods depending on the structure.

"Vertebral cartilages form during the second month [5]. Ossification centers appear shortly after, about 7–8 weeks in the neural arches, lateral masses condyles and occipital bone, but later in the body of the axis (fifth fetal months), base of the axis (sixth fetal months), anterior arch of the atlas (first year) and tip of the dens (second year). The atlantal ring is complete about 4–7 years. In the axis, the neural arch of the axis is complete at 3 years; the dens fuses with the body before 8 years and the tip of the dens before 12 years. Complete fusion of the occipital bone does not occur until adulthood [2, 6]."

PMID 21822704


An image-based skeletal tissue model for the ICRP reference newborn

Phys Med Biol. 2009 Jul 21;54(14):4497-531. Epub 2009 Jun 26.

Pafundi D, Lee C, Watchman C, Bourke V, Aris J, Shagina N, Harrison J, Fell T, Bolch W.

Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, FL, USA.

Abstract Hybrid phantoms represent a third generation of computational models of human anatomy needed for dose assessment in both external and internal radiation exposures. Recently, we presented the first whole-body hybrid phantom of the ICRP reference newborn with a skeleton constructed from both non-uniform rational B-spline and polygon-mesh surfaces (Lee et al 2007 Phys. Med. Biol. 52 3309-33). The skeleton in that model included regions of cartilage and fibrous connective tissue, with the remainder given as a homogenous mixture of cortical and trabecular bone, active marrow and miscellaneous skeletal tissues. In the present study, we present a comprehensive skeletal tissue model of the ICRP reference newborn to permit a heterogeneous representation of the skeleton in that hybrid phantom set-both male and female-that explicitly includes a delineation of cortical bone so that marrow shielding effects are correctly modeled for low-energy photons incident upon the newborn skeleton. Data sources for the tissue model were threefold. First, skeletal site-dependent volumes of homogeneous bone were obtained from whole-cadaver CT image analyses. Second, selected newborn bone specimens were acquired at autopsy and subjected to micro-CT image analysis to derive model parameters of the marrow cavity and bone trabecular 3D microarchitecture. Third, data given in ICRP Publications 70 and 89 were selected to match reference values on total skeletal tissue mass. Active marrow distributions were found to be in reasonable agreement with those given previously by the ICRP. However, significant differences were seen in total skeletal and site-specific masses of trabecular and cortical bone between the current and ICRP newborn skeletal tissue models. The latter utilizes an age-independent ratio of 80%/20% cortical and trabecular bone for the reference newborn. In the current study, a ratio closer to 40%/60% is used based upon newborn CT and micro-CT skeletal image analyses. These changes in mineral bone composition may have significant dosimetric implications when considering localized marrow dosimetry for radionuclides that target mineral bone in the newborn child.

PMID: 19556686

High and low birth weight and its implication for growth and bone development in childhood and adolescence

J Pediatr Endocrinol Metab. 2009 Jan;22(1):19-30.

Fricke O, Semler O, Stabrey A, Tutlewski B, Remer T, Herkenrath P, Schoenau E.

Children's Hospital, University of Cologne, Cologne, Germany. Abstract AIM: To investigate the relationship of birth weight (BW) to anthropometric measures, local body composition and bone development.

POPULATION AND METHODS: 284 individuals (age 5-19 yr, 145 females) were recruited from the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study. Parameters of bone development (cortical bone mineral density [BMDcort], endosteal circumference [CE]) and of local body composition (cross-sectional fat area [FA]) were analyzed by pQCT at the forearm. Parameters were transformed into SD scores to adjust for age or height.

RESULTS: BW predicted weight-SDS (R = 0.221), height-SDS (R = 0.260) and FA-SDS (R = 0.150). Individuals with lower BW (< 10th percentile) had lower weight-SDS (p < 0.01), height-SDS (p < 0.01), BMDcort-SDS (p = 0.02) and higher CE-SDS (p = 0.05). BMDcort was correlated with BW (r = -0.319) and FA (r = -0.283) in pubertal females.

CONCLUSION: BW is characterized by direct and indirect effects on growth, body composition and bone development.

PMID: 19344071


Growth and bone development

Nestle Nutr Workshop Ser Pediatr Program. 2008;61:53-68.

Cooper C, Harvey N, Javaid K, Hanson M, Dennison E.

MRC Epidemiology Resource Centre and Centre for Developmental Origins of Health and Adult Disease, University of Southampton, Southampton General Hospital, Southampton, UK. Abstract Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterized in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content, but not volumetric bone density, than girls. Furthermore, there is a dissociation between the peak velocities for height gain and bone mineral accrual, in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the hypothalamicpituitary-adrenal and growth hormone/insulin-like growth factor-1 axes. Maternal smoking, diet (particularly vitamin D deficiency), and physical activity also appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth are directly linked to the later risk of hip fracture. The optimization of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.

PMID: 18196944


International Workshop on the Skeletal Growth Plate Stevenson, Washington June 11–15, 2006

The Workshop was considered a significant success. Many new ideas and concepts were presented. For example, two cellular structures were described that appear to influence growth plate chondrocyte behavior. The first are actin-based signaling hubs that are activated by integrins; the second are calcium channels formed from polycystin-1 and polycystin-2 at the base of cilia. The output from these functional structures may influence cell orientation in the postmitotic phase of chondrocyte maturation. Renewed interest in vascular access to the growth plate including a rediscovered perichondrial capillary bed that surrounds the growth plate provides a fresh view of how circulating and perichondrial growth factors physically reach growth plate cells. This finding has important implications for growth plate therapeutics in the future.

Several new insights were gained into the potential interplay between growth plate regulatory circuits. For example, genetic interactions between Sox9, Sox5 and Sox 6 and between Sox9 and Runx2, were better defined, allowing one to envision how chondrocyte proliferation and terminal differentiation are coordinated and fine-tuned. Continuing on the theme of pathway integration, evidence was presented that both Smad-dependent and Smad-independent BMP pathways are involved in regulating the Ihh/PTHrP circuitry, that BMPs exert their effects on chondrogenesis through retinoic acid intermediates and also through activation of Sox9, Sox 5 and Sox6, and that canonical Wnt signaling acts through altering Ihh expression to influence chondrocyte maturation.

New approaches for keeping track of the human chondrodysplasias that integrate developmental, clinical, genetic and pathological observations were presented. Disturbances responsible for these disorders are now beginning to be understood at the molecular level. For instance, failure to hydroxylate proline residues at the 3 position of type I collagen leads to recessive osteogenesis imperfecta, and induction of the unfolded protein response to mutant type X collagen and COMP contributes to the pathogenesis of Schmid metaphyseal dysplasia, pseudoachondroplasia and multiple epiphyseal dysplasia. Similarly, delineating the intersection of two signaling pathways, the pathway downstream of the CNP receptor, which is mutated in acromesomelic dysplasia, and the pathway downstream from FGFR3, which is mutated in achondroplasia, provides a conceptual basis for treatment of achondroplasia. Mutations are being found in more and more of the genes that play important roles in growth plate development and function. Similarly, a growing number of human chondrodysplasias are being modeled through genetic engineering in mice.

Several new research tools were presented including genetically engineered mice that allow specific events important to growth plate formation and function to be dissected. Of particular note were new mouse strains harboring osterix-cre-ERT2, collagen I (3/2kb)-cre and Col10-LacZ transgenic reporter mice. A number of new analytical techniques were discussed, including real-time multiphoton imaging of growth plate and articular cartilage of live mice, microsurgical techniques to dissect and transplant rodent growth plate zones, three-dimensional culture systems to study interactions between cartilage and vascular cells, and improved high-resolution imaging technologies to assess bone structure and mineralization in mice.

The abstracts of the poster sessions are available at


Studies on the time frame for ossification of the medial clavicular epiphyseal cartilage in conventional radiography

Int J Legal Med. 2004 Feb;118(1):5-8. Epub 2003 Oct 8.

Schmeling A, Schulz R, Reisinger W, Mühler M, Wernecke KD, Geserick G.

Institut für Rechtsmedizin, Universitätsklinikum Charité der Humboldt-Universität zu Berlin, Hannoversche Strasse 6, 10015 Berlin, Germany.


Radiological assessment of the degree of ossification of the medial clavicular epiphyseal cartilage plays a vital part in forensic age diagnosis of living adolescents and young adults. A total of 873 plain chest radiographs requested by the staff medical officer for members of staff aged 16-30 at the University Hospital Charité were evaluated retrospectively. Of these X-rays 699 permitted an assessment of ossification of at least 1 side of the clavicle. In addition to the customary stages (1: non-ossified epiphysis, 2: discernible ossification centre, 3: partial fusion, 4: total fusion) a stage 5 was also defined, characterised by the disappearance of the epiphyseal scar following total fusion. The earliest age at which stage 3 was detected in either gender was 16 years. Stage 4 was first observed in women at 20 years and in men at 21 years. In both genders, the earliest observation of stage 5 was at 26 years. It was concluded that plain chest radiographs can essentially be used to assess clavicular ossification. In practice, if overlap in posterior-anterior views impedes evaluation, a lateral view should also be taken to facilitate age estimation. In forensic practice the reference values of the present paper should be applied.

PMID: 14534796

Variation in longitudinal diaphyseal long bone growth in children three to ten years of age

Am J Hum Biol. 2004 Nov-Dec;16(6):648-57.

Smith SL, Buschang PH.

Department of Sociology and Anthropology, University of Texas at Arlington, Arlington, Texas 76019, USA. <>

Abstract Data from the Child Research Council (Denver, CO) were analyzed to model longitudinal growth changes in the humerus, radius, femur, and tibia in 31 boys and 36 girls between 3 and 10 years of age. Multilevel modeling of growth changes allowed efficient estimates of bone size and bone growth variation to be obtained as well as comparisons of growth patterns within and between limbs. The long bones displayed decelerating growth through time, with greater velocities for the larger lower limb (vs. smaller upper limb) bones and the larger proximal (vs. smaller distal) elements within limbs. Coordination for bone size and growth velocity is good both within and between limbs, suggesting a common growth control mechanism that should make growth prediction possible. Adjusted for size, the tibia appears to be the most variable of these four long bones, which may be due to a combination of environmental effects and flexible growth potential.

(c) 2004 Wiley-Liss, Inc. PMID: 15495231