Human iliac crest cancellous bone elastic modulus and hardness differ with bone formation rate per bone surface but not by existence of prevalent vertebral fracture

As part of an experiment to study the role of corticosteroids in bone changes during spaceflight, male Sprague-Dawley rats (6 wk old, 165 g body weight) were placed in orbit for 17 days, in groups of six, in animal-enclosure modules (AEMs) aboard the space shuttle Columbia (STS-78). Control rats were group housed in a similar manner in ground-based AEMs or standard vivarium cages. Adrenal hypertrophy occurred in flight rats, but bone histomorphometric analyses revealed a lack of significant changes in bone mass and bone formation in these animals. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were nearly the same in flight and ground-based rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral necks of flight rats. In the tibial diaphysis, periosteal bone formation rate was found to be identical in flight and ground-based rats. The results indicate that, under conditions of group housing in AEMs, spaceflight has minimal effects on bone mass and bone formation in rapidly growing rats. These findings emphasize the need to investigate the importance of rat age, strain, and especially housing conditions for studies of the skeletal effects of spaceflight.

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Effects of disrupted β1-integrin function on the skeletal response to short-term hindlimb unloading in mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00689.2004 ◽

2005 ◽

Vol 98 (2) ◽

pp. 690-696 ◽

Cited By ~ 23

Author(s):

U. T. Iwaniec ◽

T. J. Wronski ◽

D. Amblard ◽

Y. Nishimura ◽

M. C. H. van der Meulen ◽

...

Keyword(s):

Bone Formation ◽

Cancellous Bone ◽

Formation Rate ◽

Dominant Negative ◽

Hindlimb Unloading ◽

Femoral Diaphysis ◽

Short Term ◽

Bone Formation Rate ◽

Mechanical Unloading ◽

Lumbar Vertebral Body

The study was designed to determine whether β1-integrin plays a role in mediating the acute skeletal response to mechanical unloading. Transgenic (TG) mice were generated to express a dominant negative form of β1-integrin under the control of the osteocalcin promoter, which targets expression of the transgene to mature osteoblasts. At 63 days of age, wild-type (WT) and TG mice were subjected to hindlimb unloading by tail suspension for 1 wk. Pair-fed, normally loaded WT and TG mice served as age-matched controls. Bone samples from each mouse were processed for quantitative bone histomorphometry and biomechanical testing. The skeletal phenotype of TG mice was characterized by lower cancellous bone mass in the distal femoral metaphysis (−52%) and lumbar vertebral body (−20%), reduced curvature of the proximal tibia (−20%), and decreased bone strength (−20%) and stiffness (−23%) of the femoral diaphysis with relatively normal indexes of cancellous bone turnover. Hindlimb unloading for only 1 wk induced a 10% decline in tibial curvature and a 30% loss of cancellous bone in the distal femur due to a combination of increased bone resorption and decreased bone formation in both WT and TG mice. However, the strength and stiffness of the femoral diaphysis were unaffected by short-term hindlimb unloading in both genotypes. The observed increase in osteoclast surface was greater in unloaded TG mice (92%) than in unloaded WT mice (52%). Cancellous bone formation rate was decreased in unloaded WT (−29%) and TG (−15%) mice, but, in contrast to osteoclast surface, the genotype by loading interaction was not statistically significant. The results indicate that altered integrin function in mature osteoblasts may enhance the osteoclastic response to mechanical unloading but that it does not have a major effect on the development of cancellous osteopenia in mice during the early stages of hindlimb unloading.

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Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone

Journal of Applied Physiology ◽

10.1152/japplphysiol.01622.2005 ◽

2006 ◽

Vol 101 (3) ◽

pp. 881-886 ◽

Cited By ~ 39

Author(s):

Russell T. Turner ◽

Sutada Lotinun ◽

Theresa E. Hefferan ◽

Emily Morey-Holton

Keyword(s):

Parathyroid Hormone ◽

Bone Formation ◽

Cancellous Bone ◽

Therapeutic Dose ◽

Weight Bearing ◽

Formation Rate ◽

Hindlimb Unloading ◽

Male Rats ◽

Mineral Apposition Rate ◽

Bone Formation Rate

Intermittent treatment with parathyroid hormone (PTH) increases bone formation and prevents bone loss in hindlimb-unloaded (HLU) rats. However, the mechanisms of action of PTH are incompletely known. To explore possible interactions between weight bearing and PTH, we treated 6-mo-old weight-bearing and HLU rats with a human therapeutic dose (1 μg·kg−1·day−1) of human PTH(1–34) (hPTH). Cortical and cancellous bone formation was measured in tibia at the diaphysis proximal to the tibia-fibula synostosis and at the proximal metaphysis, respectively. Two weeks of hindlimb unloading resulted in a dramatic decrease in the rate of bone formation at both skeletal sites, which was prevented by PTH treatment at the cancellous site only. In contrast, PTH treatment increased cortical as well as cancellous bone formation in weight-bearing rats. Two-way ANOVA revealed that hPTH and HLU had independent and opposite effects on all histomorphometric indexes of bone formation [mineral apposition rate (MAR), double-labeled perimeter (dLPm), and bone formation rate (BFR)] at both skeletal sites. The bone anabolic effects of weight bearing and hPTH on dLPm and BFR at the cortical site were additive, as were the effects on MAR at the cancellous site. In contrast, weight bearing and hPTH resulted in synergistic increases in cortical bone MAR and cancellous bone dLPm and BFR. We conclude that weight bearing and PTH act cooperatively to increase bone formation by resulting in site-specific additive and synergistic increases in indexes of osteoblast number and activity, suggesting that weight-bearing exercise targeted to osteopenic skeletal sites may improve the efficacy of PTH therapy for osteoporosis.

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Characterization of osteogenic response to mechanical stimulation in cancellous bone of rat caudal vertebrae

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.265.2.e340 ◽

1993 ◽

Vol 265 (2) ◽

pp. E340-E347 ◽

Cited By ~ 8

Author(s):

J. W. Chow ◽

C. J. Jagger ◽

T. J. Chambers

Keyword(s):

Bone Formation ◽

Cancellous Bone ◽

Mechanical Stimulation ◽

Formation Rate ◽

Caudal Vertebra ◽

Bone Formation Rate ◽

Caudal Vertebrae ◽

Osteogenic Response ◽

Old Rats

We have recently developed an experimental model in which pins, inserted into the 7th and 9th caudal vertebrae of 13-wk-old rats, are used to load the 8th caudal vertebra in compression. We have now applied this model to assess the responsiveness of rat cancellous bone to mechanical stimulation. We found that daily exposure to loads that induce strains similar to those observed in bone during relatively gentle physical activity, for 30 cycles/day, increased the rate of lamellar bone formation on cancellous surfaces by up to 140-fold. Bone formation rate showed a highly significant (P < 0.0001) correlation with the number of days for which the bones were loaded and with the size of the load. A single loading episode of 300 cycles, representing a 10-min period of loading, increased bone formation to 24 times that in nonloaded controls. Indexes of bone resorption were essentially the inverse of the bone formation parameters. These experiments show that rat cancellous bone is exquisitely sensitive to mechanical stimulation and suggest that the mechanical environment is a major determinant of the physiological behavior of mammalian cancellous bone.

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Unusual Histomorphometric Changes in the Iliac Crest in Ovariectomized and Sham-operated Ewes

Veterinary and Comparative Orthopaedics and Traumatology ◽

10.1055/s-0038-1632453 ◽

1995 ◽

Vol 08 (04) ◽

pp. 184-190

Author(s):

A. R. Villanueva ◽

M. R. Alvis ◽

H. M. Aberman ◽

A. S. Turner

Keyword(s):

Bone Loss ◽

Bone Formation ◽

Cancellous Bone ◽

Formation Rate ◽

Large Animal Model ◽

Seasonal Effect ◽

Sham Operation ◽

Large Animal ◽

Bone Formation Rate ◽

Oestrogen Deficiency

SummaryA large animal model to study cancellous bone loss and the effect of various therapeutic agents following oestrogen deficiency-related bone loss is needed. Following double fluorochrome labeling at the time of surgery, six and 12 months later, static and dynamic histomorphometry was performed on undecalcified sections of the iliac crests of 16 mature (4 to 5-yearold) ewes following ovariectomy (OVX; n = 8) or sham-operation (Sham; n = 8). We found a slight decrease in bone mass associated with oestrogen deficiency as indicated by a statistically significant increase in trabecular separation (Tb.Sp: +14%, p <0.05) and decrease in wall thickness (W.Th: -10%, p <0.05) in the OVX group. However, at six months, we saw evidence of complete cessation of bone formation in both OVX and Sham animals. At that time there was a statistically significant (p <0.05) decline in the following parameters in both the Sham and OVX animals respectively: osteoid surface (OS: -79%, -77%), osteoid thickness (O.Th: -40%, -30%), flat osteoblasts (Fl.Ob.S: -87%, -94%), cuboidal osteoblasts (Cu.Ob.S: -88%, -65%), osteoid surface as a percentage of the total cancellous bone perimeter (OS/BS: -82%, -80%), osteoblast surface as a percentage of total cancellous bone surface (Ob.S/BS: -94%, -77%), mineralizing surface as a percentage of double labels plus half single labels (MS/OS: -44%, -42%), osteoid volume as a percentage of total area of mineralized bone plus osteoid (OV/TV: -88%, -88%), osteoid as a percentage of mineralized bone (OV/BV: -87%, -86%), osteoid maturation time (Omt: -27%, -35%), bone formation rate, surface referent (BFR/BS: -90%, -87%), bone formation rate, volume referent (BFR/BV: -89%, -86%), and bone formation rate, tissue referent (BFR/TV: -91%, -88%). The data was compared to static and dynamic histomorphometry of three intact ewes (similar age, breed, source) whose biopsies were taken two months after the second biopsies in the present study. The data indicate that there is a slight loss of trabecular bone following OVX but we are unable to explain the dramatic depression of bone turnover with little change in bone resorption. The data resembles the response seen when sheep are given daily doses of methylprednisolone. We speculate that this phenomenon may be a response to endogenous corticosteroid release in a response to stresses of transport, and surgery. A seasonal effect may be another explanation fro these changes, whereas dietary alteration (e. g. poisonous plants), hormonal changes or response to changes in physical activity are unlikely causes.A large animal model to study cancellous bone loss and effect of various therapeutic agents following oestrogen deficiency – related bone loss is needed. Following double fluorochrome labeling at the time of surgery, six and 12 months later, static and dynamic histomorphome-try was performed on undecal-cified sections of the iliac crests of 16 mature (4 to 5-year-old) ewes following ovariectomy (OVX; n = 8) or sham-operation (Sham; n = 8). A slight decrease in bone mass associated with oestrogen deficiency was seen but there was also evidence of complete cessation of bone formation in both OVX and Sham animals. The data resembles the responses seen when sheep are given daily doses of methylpednisolone and may be a response to endogenous corticosteroid release. A seasonal effect may be another explanation for these changes, whereas dietary alteration (e. g. poisonous plants), hormonal changes or response to changes in physical activity are unlikely causes.

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Relationships between osteocyte density and bone formation rate in human cancellous bone

Bone ◽

10.1016/s8756-3282(02)00907-9 ◽

2002 ◽

Vol 31 (6) ◽

pp. 709-711 ◽

Cited By ~ 71

Author(s):

S Qiu ◽

D.S Rao ◽

S Palnitkar ◽

A.M Parfitt

Keyword(s):

Bone Formation ◽

Cancellous Bone ◽

Formation Rate ◽

Bone Formation Rate ◽

Human Cancellous Bone ◽

Osteocyte Density

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Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density

Acta Orthopaedica ◽

10.3109/17453674.2011.566138 ◽

2011 ◽

Vol 82 (2) ◽

pp. 228-233 ◽

Cited By ~ 23

Author(s):

Ola Belfrage ◽

Gunnar Flivik ◽

Martin Sundberg ◽

Uldis Kesteris ◽

Magnus Tägil

Keyword(s):

Bone Density ◽

Bone Formation ◽

Cancellous Bone ◽

Formation Rate ◽

Local Treatment ◽

Bone Grafts ◽

Bone Formation Rate

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Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.76.3.111 ◽

2006 ◽

Vol 76 (3) ◽

pp. 111-116 ◽

Cited By ~ 3

Author(s):

Hiroshi Matsuzaki ◽

Misao Miwa

Keyword(s):

Bone Formation ◽

Calcium Supplementation ◽

Control Diet ◽

Formation Rate ◽

Dietary Calcium ◽

Mineral Apposition Rate ◽

Control Group ◽

Deficient Diet ◽

Bone Formation Rate ◽

Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

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