Make No Bones about It: Long Bones Scale Isometrically.

Long bones are far from being simple cylinders, so how is the relative positioning of their various features maintained during growth? A new study shows that growth is isometric and that drift from the correct position is minimized. Read the Research Article.

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.

The performance of second trimester long bone ratios for Down syndrome screening is influenced by gestational age.

OBJECTIVE: To determine if gestational age (GA) at the time of ultrasound impacts the positive predictive value of shortened femur and humerus lengths (FL, HL) for trisomy 21 (T21). METHODS: Sonograms from 14 to 21 and 6/7 weeks' gestation were collected over a 28 month period. Multiple gestations or fetuses with major structural anomalies were excluded. Biometric data and GA were obtained; the expected HL (or FL): observed HL (or FL) ratios were calculated using two regression formulas (Benacerraf and Nyberg). A HL ratio <0.90 and a FL ratio <0.91 were considered shortened. T21 fetuses were identified through database and chart review. Positive predictive values (PPV) for T21 of the shortened bone ratios were determined, then stratified by GA. RESULTS: Of the 2606 ultrasounds, 8.9% and 18.9% of fetuses had shortened HL and FL ratios, respectively, using the Benacerraf formula. Shortened ratios were noted significantly less commonly (2.3 and 4.4%, respectively, P < 0.001 for each) using the Nyberg formula. With either formula, abnormal bone ratios were more frequently documented with a GA less than 17 weeks (P < 0.001). There were 17 T21 pregnancies. CONCLUSIONS: GA and formula selection influence the performance of long bone ratios as soft markers for T21 in the second trimester.