Age-related changes in iliac crest cortical width and porosity: a histomorphometric study

Authors

Shobna Vedi, Stephen Kaptoge, J. E. Compston

Abstract

Although age-related changes in cancellous bone structure in human are relatively well characterized, few studies have addressed changes in cortical bone. We have investigated age-related changes in iliac crest bone biopsy specimens from 54 normal subjects, 23 men and 31 women, aged 18–90 years. A significant decrease in cortical width and area was seen (P = 0.002 and < 0.001 respectively), with no difference between sexes. Haversian canal density increased significantly with age by approximately 9% per decade (P = 0.032) but Haversian canal area tended to be lower, resulting in no overall age-related difference in cortical porosity. Haversian canal area was significantly higher in the endosteal section than in the periosteal section of the cortex (P = 0.019) but the Haversian canal density was lower, resulting in similar overall porosity in the two sections. In conclusion, our results demonstrate an age-related decrease in iliac crest cortical width in men and women and an increase in Haversian canal density, but no overall change in cortical porosity.

Link to Article

http://dx.doi.org/10.1111/j.1469-7580.2011.01356.x

Biofunctionalization of titanium implants with a biomimetic active peptide (P-15) promotes early osseointegration

Authors

R. Lutz, S. Srour, J. Nonhoff, T. Weisel, C. J. Damien, K. A. Schlegel

Abstract

The early stages of peri-implant bone formation play an essential role in the osseointegration and long-term success of dental implants. By incorporating bioactive coatings, this biofunctionalization of implant surfaces may enhance the attachment of the implant to the surrounding bone and stimulate bone regeneration. Material and methods: To demonstrate faster osseointegration, the surfaces of dental implants were grit-blasted and acid-etched. They were then coated with hydroxyapatite (HA) and experimental implants were further coated with a biomimetic active peptide (P-15) in one of two concentrations. These biofunctionalized samples and controls with no peptide were placed in the forehead region of 12 adult pigs. Six animals were evaluated for a period of 14 or 30 days. Histomorphometric analysis demonstrated that the implants with the high concentration of P-15 had significantly higher percentage of bone-to-implant contact (BIC) at 14 (P=0.018) and 30 (P=0.015) days compared with the other groups. Both concentrations of P-15 showed increased peri-implant bone density compared to the control group at 30 days. Biofunctionalization of the implant surface with a biomimetic active peptide leads to significantly increased BIC rates at 14 and 30 days and higher peri-implant bone density at 30 days.

Link to Article

http://dx.doi.org/10.1111/j.1600-0501.2009.01904.x

Blockade of transforming growth factor-beta (TGFβ) signaling inhibits osteoblastic tumorigenesis by a novel human prostate cancer cell line

Authors

Sweta Mishra, Yuping Tang, Long Wang, Linda deGraffenried, I-Tien Yeh, Sherry Werner, Dean Troye, John A. Copland, Lu-Zhe Sun

Abstract

The skeleton is the most common site of prostate cancer metastasis, which often results in osteoblastic lesions. The role of transforming growth factor-beta (TGFβ) signaling in prostate cancer-induced osteoblastic metastasis is not clear. We investigated the role of TGFβ signaling in prostate cancer-induced bone metastasis using a novel human prostate cancer cell line, PacMetUT1. We injected PacMetUT1/Luc-GFP cells in male nude mice by intracardiac and intratibia injections and then investigated the effect of TGFβ signaling abrogation on osteoblastic tumor growth and incidence in vivo by using fluorescence and bioluminescence imaging analysis and quantifying bone and tumor volume by histomorphometry analysis. Osteoclasts were counted using TRAP assay. Osteoblastic bone metastasis in skull, rib, and femur was detected after 10–16 weeks of intracardiac injection of the PacMetUT1 cells. Stable knockdown of TGFβ1 with an shRNA resulted in decreased tumor incidence and bone formation when the cells were directly injected into the tibiae. Systemic administration of either a small inhibitor of TGFβ type I receptor kinase or a pan TGFβ binding protein (BGERII) also decreased bone tumor growth and osteoblastic bone formation in vivo after 7 weeks of treatment. Our results for the first time indicate that blockade of TGFβ signaling in the PacMetUT1 model significantly inhibits osteoblastic bone formation and tumor incidence. Thus, TGFβ signaling pathway may be a viable target for the prevention and treatment of prostate cancer-induced bone metastasis

Link to Article

http://dx.doi.org/10.1002/pros.21361

Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: An in vivo micro CT study

Authors

Sander M. Botter, Gerjo J.V.M van Osch, Stefan Clockaerts, Jan H. Waarsing, Harrie Weinans, Johannes P.T.M. van Leeuwen

Abstract

In osteoarthritis (OA) changes occur both in cartilage and subchondral bone. The subchondral bone plate facilitates normal crosstalk between articular cartilage and trabecular subchondral bone, and adaptive changes in the plate due to OA may therefore disturb crosstalk homeostasis. To investigate these changes over time we examined the cartilage-subchondral bone interface using a combined approach of histology and in vivo micro CT. Male C57Bl/6 mice (n=8), aged 16 weeks, received intra-articular injections with collagenase in one joint to induce instability-related OA and saline into the contralateral knee joint (controls). At 2, 4, 6, 10 and 14 weeks post-injection, changes in the tibial subchondral bone plate and subchondral trabeculae were analyzed. At two weeks post-injection, collagenase injected joints had significantly more cartilage damage and osteophytosis than control joints. Osteoclast activity directly underneath the subchondral bone plate was significantly elevated (Oc.S./BS controls: 7.60± 0.81%; OA: 11.07± 0.79%), causing the plate to become thinner and creating a large increase in subchondral bone plate porosity (cumulative porosity volume controls: 0.05e-3 ± 0.04e-3 mm3; OA: 2.52e-3 ± 0.69e-3 mm3). At four weeks post-injection, the previously formed perforations disappeared, coinciding with a significant rise in osteoblast activity in the subchondral trabecular bone (bone formation rate controls: 0.30± 0.03, OA: 0.62± 0.13 μm2/μm3*day). The current study provides for the first time quantitative longitudinal data on the dynamic changes in the subchondral bone plate after OA induction. The development of plate perforations may enhance mutual interaction between subchondral trabeculae, bone marrow cells and the articular cartilage in OA.

Link to Article

http://dx.doi.org/10.1002/art.30307

Depth of subchondral perforation influences the outcome of bone marrow stimulation cartilage repair

Authors

Hongmei Chen, Caroline D. Hoemann, Jun Sun, Anik Chevrier, Marc D. McKee, Matthew S. Shive, Mark Hurtig, Michael D. Buschmann

Abstract

Subchondral drilling and microfracture are bone marrow stimulation techniques commonly used for the treatment of cartilage defects. Few studies to date have examined the technical variants which may influence the success of the cartilage repair procedures. This study compared the effect of hole depth (6 mm vs. 2 mm) and hole type (drill vs. microfracture) on chondral defect repair using a mature rabbit model. Results from quantitative histomorphometry and histological scoring showed that deeper versus shallower drilling elicited a greater fill of the cartilage defect with a more hyaline character in the repair matrix indicated by significant improvement (p = 0.021) in the aggregate measure of increased cartilage defect fill, increased glycosaminoglycan and type II collagen content and reduced type I collagen content of total soft repair tissue. Compared to microfracture at the same 2 mm depth, drilling to 2 mm produced a similar quantity and quality of cartilage repair (p = 0.120) according to the aggregate indicator described above. We conclude that the depth of bone marrow stimulation can exert important influences on cartilage repair outcomes

Link to Article

http://dx.doi.org/10.1002/jor.21386

Bone biopsy findings and correlation with clinical, radiological and biochemical parameters in children with fractures

Authors

Mervi K Mäyränpää, Inari S Tamminen, Heikki Kröger, Outi Mäkitie

Abstract

In children the diagnosis of osteoporosis is based on fracture history and DXA-derived BMD. Bone biopsy is an invasive but accurate method to study bone characteristics. In this study we evaluated bone biopsy findings and their correlation with non-invasive measures of bone health. Transiliac bone biopsy was performed on 24 consecutive children (17 boys, median age 12 years, range 6-16 years) evaluated for suspected primary osteoporosis. Biopsy findings were compared with normative data and correlated with clinical, radiological, biochemical, and densitometric findings. The patients had sustained altogether 64 non-vertebral fractures (median 2.5) from low- or moderate-energy traumas, and 14 patients (58%) had vertebral fractures. The median lumbar spine BMD Z-score was –1.2 (range -3.1 to +1.0). Hypovitaminosis D was present in 58%. Histomorphometry showed low bone volume in 7 patients and normal bone volume in 17. Bone turnover was high in 7, low in 7, and normal in 10 patients. Histomorphometric findings correlated poorly with fracture history, serum bone turnover markers and DXA findings. Vitamin D deficiency and low lumbar BMD were associated with high bone turnover in the biopsy. These findings underscore the difficulties in diagnosing pediatric osteoporosis. Bone histomorphometry gives additional information and may be useful when considering bisphosphonate treatment in children with suspected primary osteoporosis.

Link to Article

http://dx.doi.org/10.1002/jbmr.373