Mammalian enamel formation is periodic, including fluctuations attributable to the daily biological clock as well as longer-period oscillations that enigmatically correlate with body mass. Because the scaling of bone mass to body mass is an axiom of vertebrate hard tissue biology, we consider that long-period enamel formation rhythms may reflect corresponding and heretofore unrecognized rhythms in bone growth. The principal aim of this study is to seek a rhythm in bone growth demonstrably related to enamel oscillatory development. Our analytical approach is based in morphology, using a variety of hard tissue microscopy techniques. We first ascertain the relationship among longperiod enamel rhythms, the striae of Retzius, and body mass using a large sample of mammalian taxa. In addition, we test whether osteocyte lacuna density (a surrogate for rates of cell proliferation) in bone is correlated with mammalian body mass. Finally, using fluorescently labeled developing bone tissues, we investigate whether the bone lamella, a fundamental microanatomical unit of bone, relates to rhythmic enamel growth increments. Our results confirm a positive correlation between long-period enamel rhythms and body mass and a negative correlation between osteocyte density and body mass. We also confirm that lamellar bone is an incremental tissue, one lamella formed in the species-

Bone exhibits positive form birefringence dominated by and dependent upon the orientation of its collagen. The biomechanical efficacy of bone as a tissue is largely determined by collagen fibers of preferred orientation and distribution (and corresponding orientation of mineral crystallites), and evidence is accumulating to demonstrate that this efficacy extends to function at the organ level. This study has three aims. The first is to provide a background to the study of circularly polarized light (CPL) investigations of collagen fiber orientation in bone. The significance of preferred collagen fiber orientation in bone, linearly polarized light and CPL imaging principles, and a short history of CPL studies of mammalian functional histology are reviewed. The second is to describe, in some detail, methodological considerations relating to specimen preparation and imaging appropriate for the quantitative analysis of preferentially oriented collagen. These include section transparency, section thickness, the uniformity of the illuminating system, and CPL paraphernalia. Finally, we describe a grey-level standard useful for quantitative CPL, based upon mineralized turkey tendon, which shall be provided to investigators upon request. When due consideration is paid to specimen preparation and imaging conditions, quantitative assessment of collagen fiber orientation provides insight into the effects of mechanical loading on the skeleton. Anat Rec (Part B: New Anat) 274B: 157-168, 2003.

Abaloparatide, a novel analog of parathyroid hormone‐related protein (PTHrP 1–34), became in 2017 the second osteoanabolic therapy for the treatment of osteoporosis. This study aims to compare the effects of PTH (1‐34), PTHrP (1‐36), and abaloparatide on bone remodeling in male mice. Intermittent daily subcutaneous injections of 80 μg/kg/d were administered to 4‐month‐old C57Bl/6J male mice for 6 weeks. During treatment, mice were followed by DXA‐Piximus to assess changes in bone mineral density (BMD) in the whole body, femur, and tibia. At either 4 or 18 hours after the final injection, femurs were harvested for μCT analyses and histomorphometry, sera were assayed for bone turnover marker levels, and tibias were separated into cortical, trabecular, and bone marrow fractions for gene expression analyses. Our results showed that, compared with PTH (1‐34), abaloparatide resulted in a similar increase in BMD at all sites, whereas no changes were found with PTHrP (1‐36). With both PTH (1‐34) and abaloparatide, μCT and histomorphometry analyses revealed similar increases in bone volume associated with an increased trabecular thickness, in bone formation rate as shown by P1NP serum level and in vivo double labeling, and in bone resorption as shown by CTX levels and osteoclast number. Gene expression analyses of trabecular and cortical bone showed that PTH (1‐34) and abaloparatide led to different actions in osteoblast differentiation and activity, with increased Runx2, Col1A1, Alpl, Bsp, Ocn, Sost, Rankl/Opg, and c‐fos at different time points. Abaloparatide seems to generate a faster response on osteoblastic gene expression than PTH (1‐34). Taken together, abaloparatide at the same dose is as effective as PTH (1‐34) as an osteoanabolic, with an increase in bone formation but also an increase in bone resorption in male mice. © 2019 American Society for Bone and Mineral Research.

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Neanderthals had large and projecting (prognathic) faces similar to those of their putative ancestors from Sima de los Huesos (SH) and different from the retracted modern human face. When such differences arose during development and the morphogenetic modifications involved are unknown. We show that maxillary growth remodelling (bone formation and resorption) of the Devil's Tower (Gibraltar 2) and La Quina 18 Neanderthals and four SH hominins, all sub-adults, show extensive bone deposition, whereas in modern humans extensive osteoclastic bone resorption is found in the same regions. This morphogenetic difference is evident by ∼5 years of age. Modern human faces are distinct from those of the Neanderthal and SH fossils in part because their postnatal growth processes differ markedly. The growth remodelling identified in these fossil hominins is shared with Australopithecus and early Homo but not with modern humans suggesting that the modern human face is developmentally derived.

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Studies of variation in orientation of collagen fibers within bone have lead to the proposition that these are preferentially aligned to accommodate different kinds of load, with tension best resisted by fibers aligned longitudinally relative to the load, and compression best resisted by transversely aligned fibers. However, previous studies have often neglected to consider the effect of developmental processes, including constraints on collagen fiber orientation (CFO), particularly in primary bone. Here we use circularly polarized light microscopy to examine patterns of CFO in cross-sections from the midshaft femur, humerus, tibia, radius, and ulna in a range of living primate taxa with varied body sizes, phylogenetic relationships and positional behaviors. We find that a preponderance of longitudinally oriented collagen is characteristic of both periosteal primary and intracortically remodeled bone. Where variation does occur among groups, it is not simply understood via interpretations of mechanical loads, although prioritized adaptations to tension and/or shear are considered. While there is some suggestion that CFO may correlate with body size, this relationship is neither consistent nor easily explicable through consideration of size-related changes in mechanical adaptation. The results of our study indicate that there is no clear relationship between CFO and phylogenetic status. One of the principle factors accounting for the range of variation that does exist is primary tissue type, where slower depositing bone is more likely to comprise a larger proportion of oblique to transverse collagen fibers. Anat Rec, 300:1189-1207, 2017. © 2017 Wiley Periodicals, Inc.

Studies of facial ontogeny in immature hominins have contributed significantly to understanding the evolution of human growth and development. The recently discovered hominin species Autralopithecus sediba is represented by a well-preserved and nearly complete facial skeleton of a juvenile (MH1) which shows a derived facial anatomy. We examined MH1 using high radiation synchrotron to interpret features of the oronasal complex pertinent to facial growth. We also analyzed bone surface microanatomy to identify and map fields of bone deposition and bone resorption, which affect the development of the facial skeleton. The oronasal anatomy (premaxilla-palate-vomer architecture) is similar to other Australopithecus species. However surface growth remodeling of the midface (nasomaxillary complex) differs markedly from Australopithecus, Paranthropus, early Homo and from KNM-WT 15000 (H. erectus/ergaster) showing a distinct distribution of vertically disposed alternating depository and resorptive fields in relation to anterior dental roots and the subnasal region. The ontogeny of the MH1 midface superficially resembles some H. sapiens in the distribution of remodeling fields. The facial growth of MH1 appears unique among early hominins representing an evolutionary modification in facial ontogeny at 1.9 my, or to changes in masticatory system loading associated with diet.