Endocortical Area Research Articles

Bone Health Among Transgender Youth: What Is a Clinician to Do?

Bone Health Among Transgender Youth: What Is a Clinician to Do?

Parathyroid Hormone Remodels Bone Transitional Vessels and the Leptin Receptor-Positive Pericyte Network in Mice.

Intermittent parathyroid hormone (iPTH) is anti-osteoporotic and affects bone vessels. Transitional capillaries close to the bone surface, which express both endomucin (Edm) and CD31, bear leptin receptor-expressing (LepR) perivascular cells that may differentiate into osteoblasts. Increased numbers of type H endothelial cells (THEC; ie, Edmhi /CD31hi cells assessed by flow cytometry, FACS) are associated with higher bone formation in young mice. We hypothesized that iPTH administration impacts transitional vessels by expanding THECs. Four-month-old C57/Bl6J female mice were injected with PTH 1-84 (100 μg/kg/d) or saline (CT) for 7 or 14 days. We quantified LepR+ , CD31+ , Edm+ cells and THECs by FACS in hindlimb bone marrow, and Edm/LepR double immunolabelings on tibia cryosections. Additionally, we analyzed bone mRNA expression of 87 angiogenesis-related genes in mice treated with either intermittent or continuous PTH (iPTH/cPTH) or saline (CT) for 7, 14, and 28 days. iPTH dramatically decreased the percentage of THECs by 78% and 90% at days 7 and 14, respectively, and of LepR+ cells at day 14 (-46%) versus CT. Immunolabeling quantification showed that the intracortical Edm+ -vessel density increased at day 14 under iPTH. In the bone marrow, perivascular LepR+ cells, connected to each other via a dendrite network, were sparser under iPTH at day 14 (-58%) versus CT. iPTH decreased LepR+ cell coverage of transitional vessels only (-51%), whereas the number of LepR+ cells not attached to vessels increased in the endocortical area only (+ 49%). Transcriptomic analyses showed that iPTH consistently upregulated PEDF, Collagen-18α1, and TIMP-1 mRNA expression compared with CT and cPTH. Finally, iPTH increased immunolabeling of endostatin, a Collagen-18 domain that can be cleaved and become antiangiogenic, in both endocortical (79%) and peritrabecular transitional microvessels at day 14. Our results show that iPTH specifically remodels transitional vessels and suggest that it promotes LepR+ cell mobilization from these vessels close to the bone surface. © 2019 American Society for Bone and Mineral Research.

Small metacarpal bones of low quality in obese children

It is still not known whether fat mass excess could exert a positive effect on bone. The aim of our study was to evaluate bone strength and quality in a group of overweight and obese children and adolescents by assessing bone geometry at metacarpal bones and ultrasound at phalangeal level. This is a cross sectional observational study performed in 123 subjects, aged 11.2 ± 2.9 years. Digitalized X-rays were evaluated at the level of the 2nd metacarpal bone for the determination of the outer (D) and inner (d) diameter, cortical area (CA), medullary endocortical area (EA), metacarpal index (MI) and bone strength (Bending Breaking Resistance Index; BBRI). A total of 98 subjects underwent amplitude dependent speed of sound (Ad-SOS) and bone transmission time (BTT) assessment by phalangeal ultrasonography. SDs for each measured parameter were as follows: Males: D = -0.71 ± 0.95, d = -0·29 ± 0.86, CA = -0.69 ± 0.69, EA = -0.32 ± 0.79, Ad-SOS = -1.14 ± 0.91, BTT = -1.17 ± 1.11 and BBRI (417 ± 151 vs 495 ± 174 mm(3) ) were all significantly lower than in controls (P < 0.05). Females: D = -1.03 ± 1.06, d = -0.38 ± 0.92, CA = -0.91 ± 0.72, EA = -0.46 ± 0.79, Ad-SOS = -1.08 ± 1.11, BTT = -0.97 ± 1.07 and BBRI (342 ± 117 vs 649 ± 318 mm(3) ) were all significantly lower than in controls (P < 0.05). Obese children show an unfavourable bone geometry and a bone of low quality and reduced strength compared to controls at a nonweight bearing skeletal site. This finding seems to support a detrimental effect of fat mass on bone and explain the frequent occurrence of wrist fractures in this group of children.

Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS

AbstractRecent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean ± SEM age, 70.5 ± 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1α (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS.

CT-based accuracy of implanting custom-made endoprostheses

To optimize physiological load transfer and mechanical stability a close geometric fit between cementless stems and the bone stock is essential. To solve the problem of a geometric mismatch between the anatomic shape of the femoral canal and conventional stems custom-made implants were developed. This study determined the accuracy of implanting custom-made press-fit straight femoral stems compared to conventional cementless stems. Nine pairs of human cadaveric femurs were used to determine the extent of the endocortical area in contact with the stem. The bone-femoral component interface was measured in vitro using CT-data analysis. A software program was developed to describe the periprosthetic inner cortical bone structure, the stem surface and the proportionate implant-endosteal bone contact. The mean endosteal bone contact of both prostheses was 21.6%. The proportionate implant-endosteal bone contact for straight custom-made femoral prostheses averaged 20.98%. For the conventional cementless stems the mean proportionate contact was 22.15%. Especially in the proximal femur the desirable contact of customized implants was not achieved by closed distal press-fit. Compared to conventional straight cementless stems custom-made stems did not extend the endocortical contact area. The desirable "fit and fill" of the proximal femur was not achieved with straight custom-made femoral components in femurs of regular geometry.

Paradoxical adaptation of mature radius to unilateral use in tennis playing

The positive effects of physical activity on human bone mass have been well documented in many cross-sectional studies comparing athletes with sedentary controls as well as in longitudinal follow-up. By applying peripheral quantitative computed tomography (pQCT), which has the advantage of measuring volumetric bone mineral density (BMD) and the ability to distinguish among trabecular and cortical components, it was demonstrated that cortical BMD of the dominant arm was not greater than that of the nondominant arm. Cortical drift toward the periosteal direction and an increase in cortical thickness resulted in an improvement of mechanical characteristics of the playing arm’s midradius. An improvement in the mechanical properties of young adult bone in response to long-term exercise was therefore related to geometric adaptation, but not to an increase in BMD. The manner in which the recruitment and function of bone cells are coordinated differs between the growing and the nongrowing skeleton. In the former, modeling is the dominant mode, and in the latter it is remodeling. In the present study, the side-to-side difference of 92 middle-aged female tennis players who initiated training after bone had matured was analyzed by pQCT. The side-to-side difference detected suggested a paradoxical adaptation of the mature radius to unilateral use during tennis playing, and that tennis playing after bone had matured did not stimulate cortical drift in the periosteal direction, unlike that seen in young subjects. Unexpectedly, the cross-sectional areas (periosteal and endocortical area) of the radius were smaller in the dominant arm than in the nondominant arm in the middle-aged female players. The findings suggest that unilateral use of the arm after the third decade of life suppresses age-related changes in bone geometry.