Anabolic action of parathyroid hormone on cortical and cancellous bone differs between axial and appendicular skeletal sites in mice

The mouse is being increasingly used to study the anabolic action of parathyroid hormone (PTH) on the skeleton. The efficacy of intermittent PTH treatment on bone varies widely among tested strains of mice with differences in peak bone mass and structure. We have therefore examined the responses of skeletal sites with high or low cancellous bone mass to PTH treatment in a single strain with genetically low bone mass. Mature C57BL/6 mice were ovariectomized (ovx) or sham operated and, after 4 weeks, treated with PTH(1-34) (40 microg/kg/day, 5 days/week sc) or vehicle for 3 or 7 weeks. Two doses of fluorescent labels were given to the animals 9 and 3 days before euthanasia. Histomorphometry was performed on sections of the proximal tibia, tibial diaphysis, and vertebral body. The results indicate that 4 to 11 weeks of ovx induced a approximately 44% loss of cancellous bone in the proximal tibia and a approximately 25% loss of cancellous bone in the vertebra with impaired trabecular architecture and high bone turnover. In the intact animals, PTH increased cancellous bone volume to a greater extent in the vertebral body than in the proximal tibia, a site with lower cancellous bone volume at the outset. In the ovx mice, PTH increased cancellous bone volume to a greater extent in the vertebral body, a site displaying moderate cancellous bone loss, than in the proximal tibia, a site with severe cancellous bone loss. Conversely, the treatment added a little cortical bone to the tibia, a highly loaded site, but did not significantly increase cortical width of the vertebral body, a less loaded site. We conclude that, for intermittent PTH treatment to be maximally effective, there must be an adequate number of trabeculae present at the beginning of treatment, regardless of estrogen status. Our results also support an interaction between PTH anabolic action and mechanical loading.     

Male rodent model of age-related bone loss in men

Osteoporosis is a common occurrence in aging men. There is currently no appropriate animal model for studying age-related bone loss in men. To determine whether male Sprague-Dawley (SD) rats experience bone loss with aging and whether this rodent model is appropriate for studying age-related bone loss in men, SD rats aged 1-27 months were examined at the L-4 vertebra, the left femoral neck, and the left proximal tibia using peripheral quantitative computed tomography (pQCT) densitometry. In the L-4 vertebra of the male SD rats, cortical bone mineral content (BMC), cortical bone mineral density (BMD), and cortical bone thickness (Ct.Th) increased to a maximum at about 4 months of age and then plateaued. Vertebral cortical BMC began to decrease after about 13 months and vertebral Ct.Th began to decrease after about 9 months. By 27 months of age, vertebral cortical BMC decreased by 26.1% (p < 0.0001) and vertebral Ct.Th decreased by 31% (p < 0.0001). Vertebral cancellous BMC and vertebral cancellous BMD increased to a maximum at about 3 months of age and then declined progressively with aging after a short plateau. From 3 to 27 months of age, vertebral cancellous BMC and vertebral cancellous BMD had decreased linearly by 35.4% (p < 0.0001) and 49.4% (p < 0.0001), respectively. Both vertebral periosteal and vertebral endocortical perimeters of the L-4 vertebra of the rats increased with aging. From 9 to 27 months of age, the percent increase of vertebral endocortical perimeter (19.8%, p < 0.0001) was higher than that of vertebral periosteal perimeter (7.4%, p < 0.0001). This process was associated with a decrease with aging in vertebral Ct.Th. In addition, cancellous bone in the femoral neck and the proximal tibia began to be lost at 9 months of age and, by 27 months of age, cancellous BMC and cancellous BMD decreased by 59.7% (p < 0.0001) and 58.4% (p < 0.0001), respectively, in the femoral neck and by 72.2% (p < 0.0001) and 71.4% (p < 0.0001), respectively, in the proximal tibia. To gain further insight into the effects of aging on cancellous bone in the L-4 vertebra, histomorphometry was done on the L-4 vertebral body of animals aged 3, 6, 9, 18, and 24 months after pQCT densitometry. From 3 months of age and thereafter, cancellous bone volume (BV/TV) decreased progressively and, by 24 months, there was a decrease of 35.7% (p < 0.0001). In the L-4 vertebra, single- and double-labeled surfaces, mineral apposition rate (MAR), and bone formation rate (BFR/BS) decreased with aging. In conclusion, age-related bone loss in male SD rats started mostly from 9 months of age when bone growth had been completed. Aging male SD rats experience bone loss comparable to that seen in men. Thus, male SD rats represent an appropriate animal model of age-related bone loss in men. We recommend using male SD rats that are 9 months old as the starting age for age-related bone loss. We also suggest using the L-4 vertebra and femoral neck as the clinically relevant bone sites for determining the cause of the loss of bone, and how and whether therapeutic agents could modulate age-related bone loss in men.     

Effects of intravenous pamidronate treatment in infants with osteogenesis imperfecta: clinical and histomorphometric outcome.

Clinical and histomorphometric outcome was compared between children with OI who had received pamidronate since infancy and age-matched patients who had never received pamidronate. Pamidronate was associated with improved vertebral shape and mass, higher cortical width, increased cancellous bone volume, and suppressed bone turnover. INTRODUCTION: Observations in small patient series indicate that infants with severe osteogenesis imperfecta (OI) benefit from treatment with cyclical intravenous pamidronate. However, detailed analyses of outcome are lacking for this age group. MATERIALS AND METHODS: Clinical outcome was evaluated in 29 children with OI types I (n = 3), III (n = 14), or IV (n = 12) who started pamidronate therapy before 2 years of age (age at treatment onset: median, 6 months; range, 2 weeks to 23 months) and who had completed 3 years of treatment (total annual pamidronate dose, 9 mg/kg). They were compared with a historical control group of 29 untreated children with severe OI who were matched for OI type and age at the 3-year treatment time-point. In addition, iliac bone histomorphometry was compared between 24 pamidronate-treated patients and 24 age-matched OI patients who had not received pamidronate. RESULTS: Morphometric evaluation of lumbar vertebrae (L(1)-L(4)) showed that the shape of vertebral bodies was better preserved in pamidronate-treated patients. This was accompanied by significantly higher lumbar spine areal and volumetric BMD (+110 and +96%, respectively) and a larger vertebral bone volume (+26%) on densitometry. Regarding mobility function, the Pediatric Evaluation of Disability Inventory gross motor score was 50% greater in the pamidronate group (p < 0.001). Iliac bone histomorphometry showed 61% higher cortical width and 89% higher cancellous bone volume in pamidronate-treated patients. Bone formation rate per bone surface in the pamidronate group was only 17% that of untreated patients. CONCLUSIONS: In conclusion, this study suggests that cyclical pamidronate treatment started in infancy leads to improved bone strength and better gross motor function but also suppresses bone turnover markedly. It is therefore prudent to reserve pamidronate treatment to infant OI patients who present with a moderate to severe phenotype.     

Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure.

Histomorphometry and microCT of 51 paired iliac crest biopsy specimens from women treated with teriparatide revealed significant increases in cancellous bone volume, cancellous bone connectivity density, cancellous bone plate-like structure, and cortical thickness, and a reduction in marrow star volume. INTRODUCTION: We studied the ability of teriparatide (rDNA origin) injection [rhPTH(1-34), TPTD] to improve both cancellous and cortical bone in a subset of women enrolled in the Fracture Prevention Trial of postmenopausal women with osteoporosis after a mean treatment time of 19 months. This is the first report of a biopsy study after treatment with teriparatide having a sufficient number of paired biopsy samples to provide quantitative structural data. METHODS: Fifty-one paired iliac crest bone biopsy specimens (placebo [n = 19], 20 microg teriparatide [n = 18], and 40 microg teriparatide [n = 14]) were analyzed using both two-dimensional (2D) histomorphometry and three-dimensional (3D) microcomputed tomography (microCT). Data for both teriparatide treatment groups were pooled for analysis. RESULTS AND CONCLUSIONS: By 2D histomorphometric analyses, teriparatide significantly increased cancellous bone volume (median percent change: teriparatide, 14%; placebo, -24%; p = 0.001) and reduced marrow star volume (teriparatide, -16%; placebo, 112%; p = 0.004). Teriparatide administration was not associated with osteomalacia or woven bone, and there were no significant changes in mineral appositional rate or wall thickness. By 3D cancellous and cortical bone structural analyses, teriparatide significantly decreased the cancellous structure model index (teriparatide, -12%; placebo, 7%; p = 0.025), increased cancellous connectivity density (teriparatide, 19%; placebo, - 14%; p = 0.034), and increased cortical thickness (teriparatide, 22%; placebo, 3%; p = 0.012). These data show that teriparatide treatment of postmenopausal women with osteoporosis significantly increased cancellous bone volume and connectivity, improved trabecular morphology with a shift toward a more plate-like structure, and increased cortical bone thickness. These changes in cancellous and cortical bone morphology should improve biomechanical competence and are consistent with the substantially reduced incidences of vertebral and nonvertebral fractures during administration of teriparatide.     

Statin Given Perorally to Adult Rats Increases Cancellous Bone Mass and Compressive Strength

Recently, it has been shown that statins increased cancellous bone formation and volume in 3-month-old rats and induced a minor decrease in osteoclast number. In the present study, one-year-old female rats were given simvastatin (10 mg/kg) or placebo daily for 3 months by a gastric tube. Specimens, 2.0 mm high, were cut transversely from the 5th lumbar vertebral body. The cancellous bone core diameters within the cortical shell of each specimen were delineated by a micro-CT scanner and then the cancellous bone was compressed in a materials testing machine between an upper and a lower platen with a diameter corresponding to the diameter of the cancellous bone core of each specimen. The cancellous bone volume was determined histomorphometrically on transverse sections. The cancellous bone volume in the simvastatin group (52.7 +/- 1.6%, mean value +/- SEM) was increased by 23% compared with the placebo group (42.8 +/- 1.7%). The compressive stress of the cancellous bone from the simvastatin group (31.8 +/- 2.7 MPa) was increased by 24% compared with the placebo group (24.1 +/- 1.9 MPa). No changes were found in cortical bone mass and strength after the statin treatment. In conclusion, statin given perorally to adult rats increased cancellous bone mass and increased cancellous bone compressive strength. The cancellous bone was found to possess normal biomechanical competence after the statin treatment.     

Short-Term Prophylaxis against Estrogen Depletion-Induced Bone Loss with Calcitriol does not Provide Long-Term Beneficial Effects on Cancellous Bone Mass or Structure in Ovariectomized Rats

It was the aim of the present study to investigate whether a 2-month prophylaxis of postovariectomy bone loss with low-dose calcitriol would have long-lasting beneficial effects on cancellous bone mass or structure after its withdrawal in rats. Six-month-old female Fischer 344 rats were either ovariectomized (OVX) or sham-operated (SHAM). Groups of SHAM and OVX rats were orally treated with either 0.05 μg calcitriol/kg per day or vehicle for 2 months postovariectomy, starting immediately after ovariectomy. Thereafter, the rats were maintained without treatment for another 4 months. Half the animals in each group were killed 2 months postovariectomy; the rest of the rats were killed 6 months postovariectomy. Cancellous bone histomorphometry was performed on the first lumbar vertebral body and on the proximal tibial metaphysis. Administration of low-dose calcitriol to SHAM and OVX rats resulted in hypercalciuria, but not hypercalcemia. By 2 months postovariectomy, calcitriol treatment of OVX rats had completely prevented tibial trabecular bone loss, and had increased vertebral cancellous bone mass in SHAM and OVX rats by about 30% over the level observed in SHAM vehicle controls. However, at the end of the experiment, i.e. 4 months after withdrawal of calcitriol, cancellous bone mass and structure in both the vertebrae and the tibiae of calcitriol-treated OVX rats were almost identical to those of vehicle-treated OVX rats. We conclude that prevention of bone loss with low-dose calcitriol during the phase of acute estrogen deficiency, when bone turnover is maximally increased, does not provide long-term beneficial effects on cancellous bone mass or structure in OVX rats. If extrapolated to postmenopausal women, this study would suggest that prophylaxis against postmenopausal bone loss with short-acting antiresorptive substances during only the first few years after menopause will probably not reduce the risk of postmenopausal osteoporosis later in life.     

The effects of PTH,loading and surgical insult on cancellous bone at the bone–implant interface in the rabbit

Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic agents may lead to more successful outcomes of non-cemented joint replacements. Using a novel rabbit model of cancellous bone loading, we examined two specific questions regarding bone formation at the bone–implant interface: (1) does the administration of intermittent PTH, a potent anabolic agent, and mechanical loading individually and combined enhance the peri-implant cancellous bone volume fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on peri-implant bone volume fraction. In this model, PTH enhanced peri-implant bone volume fraction by 30% in loaded bone, while mechanical loading alone increased bone volume fraction modestly (+ 10%). Combined mechanical loading and PTH treatment had no synergistic effect on any cancellous parameters. However, a strong combined effect was found in bone volume fraction with combined surgery and PTH treatment (+ 34%) compared to intact control limbs. Adaptive changes in the cancellous bone tissue included increased ultimate stress and enhanced remodeling activity. The number of proliferative osteoblasts increased as did their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP positive osteoclasts also increased. In summary, both loading and intermittent PTH treatment enhanced peri-implant bone volume, and surgery and PTH treatment had a strong combined effect. This finding is of clinical importance since enhancing early osseointegration in the post-surgical period has numerous potential benefits.     

Proportion of human vertebral body bone that is cancellous

The concept that vertebral fractures are caused by excessive loss of cancellous bone has been challenged by a recent study (J Bone Min Res 2:221, 1987) suggesting that vertebral bodies are composed mainly of cortical bone rather than cancellous bone. To resolve disagreement we used two independent methods to quantify the proportions of cortical and cancellous bone in 400 microns thick sections of the bodies of the second lumbar vertebrae from six men (aged 21-58 years) and seven women (aged 25-58 years). Based on the ash weight of the manually dissected components, 80% of the total bone in men and 72% in women was cancellous bone. Based on computer-assisted scanning of sections with a microdensitometer, 81% of the total bone in men and 71% in women was cancellous bone. We conclude that the traditional concept is correct: the vertebral body is composed mainly of cancellous bone.     

Cancellous and cortical bone architecture and turnover at the iliac crest of postmenopausal osteoporotic women treated with parathyroid hormone 1-84

Treatment with parathyroid hormone [PTH(1-84)] increases lumbar spine bone mineral density and decreases vertebral fractures, but its effects on bone microarchitecture are unknown. We obtained iliac crest biopsies from postmenopausal osteoporotic women given placebo (n=8) or 100 microg PTH(1-84) for 18 (n=8) or 24 (n=7) months to assess cancellous and cortical bone formation and structure. At 18 months, cancellous bone volume (BV/TV) measured by microcomputed tomography and histomorphometry was 45-48% higher in subjects treated with PTH(1-84) versus placebo, a result of higher trabecular number (Tb.N) and thickness. The higher Tb.N appeared to result from intratrabecular tunneling. Connectivity density was higher and structure model index was lower, indicating a better connected and more plate-like trabecular architecture. Cancellous bone formation rate (BFR) was 2-fold higher in PTH(1-84)-treated subjects, primarily because of greater mineralizing surface. Osteoblast and osteoid surfaces were a nonsignificant 58% and 35%, respectively, higher with PTH(1-84) treatment. Osteoclast and eroded surface were unaffected by PTH(1-84). There were no effects of PTH(1-84) treatment on cortical thickness, or endocortical or periosteal BFR, but cortical porosity tended to be higher. Although cancellous BFR was lower at 24 than at 18 months, measures of cancellous and cortical bone structure were similar at both timepoints. The bone produced by PTH(1-84) had normal lamellar structure and mineralization with no abnormal histology. In conclusion, when compared with placebo, treatment of osteoporotic women with PTH(1-84) was associated with higher BV/TV and trabecular connectivity, with a more plate-like architecture, all consistent with the lower vertebral fracture incidence.     

Reduced iliac cancellous osteocyte density in patients with osteoporotic vertebral fracture.

Iliac cancellous osteocyte density declines with age, but its relationship to vertebral fracture pathogenesis is unknown. We performed iliac bone biopsy in 44 women with clinical vertebral fracture and 56 healthy women. The fracture patients had 34% fewer osteocytes but no reduction in percent occupied lacunae. Some patients destined to sustain vertebral fracture make cancellous bone with fewer osteocytes. INTRODUCTION: Patient's with vertebral fracture have less bone than appropriate healthy controls, but other factors may contribute to bone fragility. Iliac cancellous osteocyte density declines with age in healthy women; we asked whether this variable differed between fracture patients and healthy controls. METHODS: Two groups of women were assembled. Forty-four (mean age, 66.2 years) had unequivocal evidence of bone fragility manifested as painful nontraumatic vertebral fracture, and 56 (mean age, 62.2 years) were skeletally healthy. All subjects underwent iliac bone biopsy. From archival embedded biopsy cores, new sections were stained with Goldner's trichrome, in which we enumerated osteocyte-occupied lacunae (stained), empty lacunae (unstained), and total lacunae per bone area. RESULTS: Cancellous osteocyte density was 34% lower in the fracture group than in the controls (p < 0.001); this difference was not a consequence of higher turnover, having less bone, or the small difference in age. The area under the receiver operating characteristic (ROC) curve for discrimination between the groups was >90% for osteocyte density and <75% for bone volume/tissue volume (BV/TV). The disease-related osteocyte deficit was accompanied by a proportionate reduction in empty lacunae and no change in percent occupied lacunae; therefore, it was not the result of premature death. Both superficial bone (<25 microm from the surface) and deep bone (>45 microm from the surface) were affected. In contrast, the age-related deficit is accompanied by an increase in empty lacunae and fall in percent osteocyte-occupied lacunae and occurs only in deep bone, but not in superficial bone. CONCLUSIONS: In some patients destined to sustain spontaneous vertebral compression fracture, iliac cancellous bone is made with fewer osteocytes than normal; the mechanism of osteocyte incorporation into bone needs more detailed study. Osteocyte deficiency could contribute to bone fragility, either by impairing the detection of fatigue microdamage or by reducing canalicular fluid flow. Current practices of defining vertebral fracture based on morphometry alone regardless of symptoms, and diagnosing osteoporosis based on bone densitometry alone regardless of fracture history, should be reexamined.     

Growth hormone increases cortical and cancellous bone mass in young growing rats with glucocorticoid-induced osteopenia.

The effects of growth hormone (GH) on linear growth, bone formation, and bone mass have been examined in glucocorticoid (GC)-injected young growing rats. Two-month-old female Wistar rats were injected for 90 days with 1, 3, 6, or 9 mg of methylprednisolone alone or in combination with 5 mg of GH. Bone mass and bone formation parameters were examined in the femoral cortical bone and in cortical bone and cancellous bone of the lumbar vertebra. GC administration dose dependently decreased growth, longitudinal growth of the vertebra, as well as the modeling drift of the cortical bone of the vertebral body and femoral diaphysis. In the vertebral cancellous bone, GC also decreased the mineralizing surface and inhibited the growth-related increase in cancellous bone volume. GH increased growth, longitudinal growth of the vertebra, as well as the modeling drift of the vertebral body and the femoral diaphysis, resulting in an increased cortical bone mass. GH also increased cancellous bone volume and the mineralizing surface of the vertebral body. In GC-injected animals, GH normalized and further increased growth, longitudinal growth, and the modeling drift of both the femoral diaphysis and the vertebral body, resulting in an increased cortical bone mass at both locations. GH also increased cancellous bone volume of the vertebral body in GC-injected animals, but GH did not, however, reverse the decreased mineralizing surface of cancellous bone induced by GC injections. In conclusion, GC administration to growing rats retards normal growth, longitudinal growth, and cortical bone modeling drift. It also decreases the cancellous bone mineralizing surface and inhibits the normal age-related increase in cancellous bone volume of the vertebral body. In the growing rat skeleton, GH can counteract these GC-induced side effects, except for the GC-induced decrease in the mineralizing surface of cancellous bone of the vertebral body, which remained unaffected by GH administration.     

不同能流密度体外冲击波对骨质疏松兔股骨髁部松质骨影响的实验研究

目的 观察不同能流密度体外冲击波对骨质疏松兔股骨髁部松质骨成骨作用的差异.方法 采用卵巢切除法(OVX)对30只5月龄雌性新西兰兔去势,5个月后建立骨质疏松模型.将所有骨质疏松兔随机分为3组,每组10只,其中一组为空白对照组(A组),一组为体外冲击波(ESW)能流密度0.28 mJ/mm~2处理组(B组),另一组为体外冲击波能流密度0.47 mJ/mm~2处理组(C组),脉冲次数均为2000次,在实验组兔右侧股骨髁部进行体外冲击波(ESW)处理.于处理后4、8周时分二批每组处死5只动物,分离右侧股骨远端,进行显微CT(micro-CT)测量分析.结果 micro-CT三维重建分析表明,不同能流密度冲击波处理后4周时B组和C组在骨组织体积比(BV/TV)、骨小梁数目(Tb.N)等指标之间的差异有统计学意义;8周时B组和C组分别在骨密度(BMD)、骨矿含量(BMC)和BV/TV、骨表面积体积比(BS/BV)、骨小梁连接密度(Connectivity Density)等指标之间的差别有统计学意义,其中C组的BMD和BMC分别较B组增高16.8%和10.6%,尽管C组在其他骨小梁立体测量学等指标方面均较B组优,但两组测量结果 的差别无统计学意义.结论 不同能流密度体外冲击波对骨质疏松局部治疗后,不同时间,其成骨作用不同,较高能流密度的体外冲击波在治疗后8周时,促进骨质疏松被处理局部骨小梁的改建、改善骨小梁的三维结构、增加骨密度作用较优.     

Deficient bone formation in idiopathic juvenile osteoporosis: a histomorphometric study of cancellous iliac bone.

Idiopathic juvenile osteoporosis (IJO), a rare cause of osteoporosis in children, is characterized by the occurrence of vertebral and metaphyseal fractures. Little is known about the histopathogenesis of IJO. We analyzed by quantitative histomorphometry iliac crest biopsies from 9 IJO patients (age, 10.0-12.3 years; 7 girls) after tetracycline labeling. Results were compared with identically processed samples from 12 age-matched children without metabolic bone disease and 11 patients with osteogenesis imperfecta type I. Compared with healthy controls, cancellous bone volume (BV) was markedly decreased in IJO patients (mean [SD]: 10.0% [3.1%] vs. 24.4% [3.8%]), because of a 34% reduction in trabecular thickness (Tb.Th) and a 37% lower trabecular number (Tb.N; p < 0.0001 each; unpaired t-test). Bone formation rate (BFR) per bone surface was decreased to 38% of the level in controls (p = 0.0006). This was partly caused by decreased recruitment of remodeling units, as shown by a trend toward lower activation frequency (54% of the control value; p = 0.08). Importantly, osteoblast team performance also was impaired, as evidenced by a decreased wall thickness (W.Th; 70% of the control value; p < 0.0001). Reconstruction of the formative sites revealed that osteoblast team performance was abnormally low even before mineralization started at a given site. No evidence was found for increased bone resorption. Compared with children with osteogenesis imperfecta (OI), IJO patients had a similarly decreased cancellous BV but a much lower bone turnover. These results suggest a pathogenetic model for IJO, in which impaired osteoblast team performance decreases the ability of cancellous bone to adapt to the increasing mechanical needs during growth. This will finally result in load failure at sites where cancellous bone is essential for stability.     

Time course of vertebral osteopenia in ovariectomized rats

Osteopenic changes in cancellous bone tissue of the first lumbar vertebral body were characterized in ovariectomized (OVX) rats as a function of time. Female Sprague Dawley rats (240 g body weight, 90 days old) were subjected to bilateral ovariectomy or sham surgery and sacrificed at various times from 0-540 days postovariectomy. The first lumbar vertebra was processed undecalcified for quantitative bone histomorphometry. Cancellous bone volume remained relatively constant in control rats at approximately 40% throughout the duration of the study. In contrast, cancellous bone volume was moderately decreased to 30-35% in OVX rats out to 180 days postovariectomy. Vertebral osteopenia became more pronounced in OVX rats at later times as cancellous bone volume declined to approximately 20% between 180 and 270 days and remained at that osteopenic level for the duration of the study. Osteoblast and osteoclast surface were highly elevated in OVX rats at 35 days, declined gradually toward control levels out to 180 days, then increased markedly at 270 days. Mineralizing surface and bone formation rate (tissue level, total surface referent) were maximally increased in OVX rats at 35-70 days before declining toward control levels at later times. However, these parameters remained significantly increased in OVX rats relative to control rats between 270 and 540 days. Mineral apposition rate was nearly identical in control and OVX rats at all time points and declined linearly with age in both groups. Our results indicate that osteopenia and increased bone turnover occur in the lumbar vertebral bodies of OVX rats, as had been previously observed in the proximal tibial metaphyses of these animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Computer simulation of trabecular remodeling using a simplified structural model

A simplified three-dimensional simulation of trabecular bone remodeling has been developed. The model utilizes 441 planar structural units to represent approximately 50 mm³ of initial bone volume with 199 basic multicellular units (BMUs). The simulation takes into account trabecular perforation in the structural model. The cases of male bone remodeling with no menopause and female bone remodeling with menopause are examined from the period of simulated age 25–80 years. Menopause is arbitrarily started at age 45 and extends for 7.5 years. Zero-, first-, and second-order BMU activation responses are employed to examine how the bone would be affected by the method of increase of BMU activation during menopause. At age 80, the female bone remodeling simulation produced a bone volume loss of approximately 49% for all three activation responses. This compared to a 38% bone volume loss for the case of no menopause. For the menopause simulations, an average of about 40% of the total bone loss was due to perforation.     

Independent and combined contributions of cancellous and cortical bone deficits to vertebral fracture risk in postmenopausal women.

Using iliac bone histomorphometry on 78 patients with vertebral fracture and 66 healthy postmenopausal women, cortical thickness discriminated at least as well as any cancellous bone structural index between the two groups. Subjects with a deficit in both cortical and cancellous bone had much greater likelihood of fracture. INTRODUCTION: Vertebral fracture is often attributed to disproportional loss of cancellous bone, but fracture patients may have deficits in cortical and cancellous bone. Accordingly, we examined the contribution of cortical and cancellous bone deficits, separately and together, to the likelihood of vertebral fracture. MATERIALS AND METHODS: Iliac bone histomorphometry was performed in 78 white woman with clinically apparent vertebral fracture, 66 healthy postmenopausal women, and 38 healthy premenopausal women. We measured cancellous bone volume (Cn.BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical bone volume (Ct.BV/TV), and cortical thickness (Ct.Th). For each variable, a value of >1 SD below the mean in premenopausal women was treated as a putative risk factor, and its association with the presence or absence of fracture was determined by OR calculated by logistic regression and by receiver operating characteristic (ROC) curve analysis. Subsets of fracture and control subjects were separately matched for Cn.BV/TV and Ct.Th. RESULTS: All structural indices differed between fracture patients and controls except Ct.BV/TV. There was a weak but highly significant correlation between Cn.BV/TV and Ct.Th in the entire group (r = 0.389, r(2) = 0.151 p < 0.001). Many control subjects had a high value for one of these variables and a low value for the other. Ct.Th., Cn.BV/TV, and Tb.N were all significantly associated with vertebral fracture (ORs, 4.4-5.8; ROC area under the curve [AUC], 0.74-0.85). In subjects matched for Cn.BV/TV, Ct.Th was reduced by 29% (OR, 5.0), and in subjects matched for Ct.Th, Cn.BV/TV was reduced by 27% (OR, 5.0). In patients with deficits in both cortical and cancellous bone, the ORs ( 28-35 ) were much higher. CONCLUSIONS: Deficits in cortical bone (reduced value for Ct.Th) and in cancellous bone (reduced values for Cn.BV/TV or Tb.N) were equally effective in discriminating between subjects with and without vertebral fracture. With a deficit in both cortical and cancellous bone, the association with vertebral fracture was much stronger. Vertebral fracture is not the result of disproportionate loss of cancellous bone in the patients as a whole, although individual patients may have relatively greater deficits in either cancellous or cortical bone.     

Trabecular Domain Factor and its Influence on the Strength of Cancellous Bone of the Vertebral Body

The effects of architectural differences on the strength of cancellous bone of the vertebral body have not been clarified. This study was aimed at determining the influence of trabecular domain factor (TDF), a new histomorphometric parameter, on the maximum compressive strength (MCS) in vertebral cancellous bone. TDF is a variation coefficient representing the ratio dispersion of the area of each trabecula (Sd) to the area of its domain (D). A Voronoi diagram was used to determine trabecular domains. The materials comprised 35 lumbar vertebral bodies obtained at autopsy from 35 subjects aged 25-83 years. A mechanical test sample (12 x 12 x 16 mm) was cut out from each right half, and two large, undecalcified, horizontal sections from each left half. The fields (144 mm2 x 2) for image analyses were symmetrical with those for mechanical test samples in the other half of the same vertebral body. Bone volume (BV/TV), Sd, and D were semiautomatically measured. BV/TV correlated negatively with TDF (r = -0.73). Multiple regression analysis revealed the contributions of BV/TV (partial r = 0.75, p < 0.001) and TDF (partial r = -0.42, p < 0.02) to MCS. The model with BV/TV and TDF predicted MCS, 1.50 +0.15 BV/TV -0.03 TDF, more accurately (R2 = 0.83) than that with BV/TV alone (r2 = 0.79). We conclude that the bone volume primarily contributes to the MCS of vertebral cancellous bones but that the influence of TDF on the fragility becomes increasingly important as the bone volume decreases.     

肱骨大结节足印区骨床新鲜化对肩袖撕裂早期疗效的影响

目的探讨肱骨大结节足印区骨床新鲜化对肩袖撕裂早期临床疗效的影响。方法将34例肩袖撕裂患者依据术中足印区新鲜化情况不同分为两组:对照组(17例)采用磨钻打磨足印区骨皮质至骨松质外露及脂肪外渗;观察组(17例)采用刨刀清理足印区瘢痕组织至极少软组织存留,但不处理骨质。比较两组疼痛VAS评分、Constant-Murley肩关节评分、ASES肩关节评分、关节活动度、术后并发症以及MRI的Sugaya标准分级。结果两组患者术后均随访3个月。术后3个月,VAS评分及MRI的Sugaya标准分级观察组均优于对照组(P<0.05),两组Constant-Murley肩关节评分、ASES肩关节评分、关节活动度及术后并发症比较差异无统计学意义(P>0.05)。结论在关节镜下行肩袖缝合术中,对肱骨大结节足印区骨床新鲜化至骨皮质层和骨松质层处理均可取得良好的早期疗效,而新鲜化至骨皮质层者在术后促进肩袖愈合及改善疼痛方面要优于新鲜化至骨松质层者。     

Unbiased estimation of vertebral trabecular connectivity in calcium-restricted ovariectomized minipigs

The topological changes in vertebral cancellous bone were estimated in vertebrae from calcium-restricted ovariectomized Sinclair S-1 minipigs, a recently described animal model of cancellous osteopenia. Connectivity was estimated using unbiased stereological principles in disector pairs of sections from the first lumbar vertebrae. Connectivity density was increased approximately twofold when compared with sham-operated minipigs fed a standard diet. These alterations in topology occurred coincident with a 25% increase in final resorption depth and a 150% increase in vertebral marrow star volume. Taken together, these changes suggest that in calcium-restricted ovariectomized minipigs, trabecular plates are transformed into rods by perforation. These changes in topology appear to be due, at least in part, to excessive resorptive cell function at the level of the bone remodeling unit. Conventional two-dimensional estimators of structural parameters of cancellous bone were not only less sensitive to these changes in topology but, in some cases, the estimates were directionally reversed.     

Growth hormone can reverse glucocorticoid-induced low bone turnover on cortical but not on cancellous bone surfaces in adult Wistar rats

We evaluated the effect of glucocorticoids (GC) and growth hormone (GH) on cortical and cancellous bone turnover in adult rats using random vertical sections giving valid measurements of bone surfaces and bone formation parameters. GH administration could reverse GC-induced osteopenia and low bone turnover of cortical bone. However, GH could not reverse the GC-induced low bone turnover of cancellous bone. METHODS: Seventy female Wistar rats, 7 months of age, were divided into five groups: (1) start control, (2) saline, (3) GC 9 mg/kg/day (Solu Medrol), (4) GH 5 mg/kg/day, and (5) GC 9 mg/kg/day + GH 5 mg/kg/day, and injected for 3 months. The vertebral body was examined using dynamic histomorphometry and biomechanical tests. Nonparametric methods were used. RESULTS: Glucocorticoid administration induced a low bone turnover state of both the cortical and cancellous bone of the vertebral body, without altering the absolute amount of bone or the biomechanical competence of the vertebral body. GH administration induced a small increase in longitudinal bone growth and ventral modeling drift. This growth increased the total amount of cortical, endocortical, and cancellous bone in the vertebra. The biomechanical competence of a 3.5-mm-high cylinder of the central vertebral body was also increased due to an increase in the amount of cortical bone, whereas the total amount of cancellous bone in the cylinder was unaltered. The cancellous bone density (CBV) was, however, increased due to thicker trabeculae probably induced by an accelerated mineral appositional rate (MAR) induced by GH. GH also increased longitudinal and ventral modeling drifts in the GC-injected animals. GH increased the amount of cortical bone and also the amount of cancellous bone close to the epiphyseal growth plate, whereas the cancellous bone volume of the central vertebral cylinder was unaffected by GH administration in GC-injected animals. GH could also increase parameters of bone formation (bone mineralizing surface (MS) and MAR) on cortical bone surfaces in GC-injected animals, whereas parameters of bone formation [MS and bone formation rates (BFR)] on cancellous bone surfaces were even lower than those of animals injected with GC alone. CONCLUSION: GH can reverse GC-induced low bone turnover on cortical but not on cancellous bone surfaces.