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PubMed2003

Comparison of biochemical markers of bone turnover and bone mineral density between hip fracture and vertebral fracture.

Bone density and the biochemical markers of bone turnover were compared between 26 hip-fracture patients and 41 vertebral-fracture patients after age adjustment to investigate whether or not type of osteoporosis differs between hip fracture and vertebral fracture. C-Terminal propepides of type I collagen (PIPC) was lower in hip fracture than vertebral fracture. The other bone formation markers (bone-specific alkaline phosphatase [ALP], osteocalcin) tended to be lower, and bone resorption markers (deoxypyridinoline, C-telopeptide crosslinking of type I collagen [CTX] tended to be higher in hip fracture compared to vertebral fracture. Mean of Z-scores of spine bone mineral density (BMD) in hip fracture and vertebral fracture were -0.461 and -0.919, respectively. Mean of Z-scores of femoral neck BMD in hip fracture and vertebral fracture were -0.994 and -0.361, respectively. All Z-scores were negative values, which means reduction of BMD compared to decade-matched controls. Z-scores of bone formation markers, such as bone-specific ALP, osteocalcin, and PIPC, were positive values in vertebral fracture, which means an increase against decade-matched controls, whereas those were negative values in hip fracture. Z-scores of bone resorption markers, such as deoxypyridinoline and CTX, were greater in hip fracture than in vertebral fracture. To express bone balance between formation and resorption in hip fracture and vertebral fracture, we calculated an uncoupling status index (USI) by the values of biochemical markers. USI of hip fracture showed a great negative value (-1.29), which indicates excess of bone resorption over formation, whereas that of vertebral fracture showed a small positive value (0.23). In conclusion, bone formation markers increase in vertebral fractures, but decrease in hip fracture. Bone resorption markers increase in both fracture, but greater increase in hip fracture.

Aged↗

PubMed2001

Early changes of bone histology and circulating markers of bone turnover after parathyroidectomy in hemodialysis patients with severe hyperparathyroidism.

AIMS: There have so far been no reports on the changes in bone histology in the early period after parathyroidectomy and autografting (PTX-AG). We investigated the effects of PTX-AG on bone histology during the initial 12 weeks after undergoing these surgical procedures. MATERIALS AND METHODS: We performed bone histomorphometry 3 times (before as well as 4 and 12 weeks after PTX-AG) in 6 patients and 2 times (before and 4 weeks after PTX-AG) in 3 hemodialysis patients. In addition, the circulating parameters of bone metabolism were also assessed before and after PTX-AG in all 9 patients. The changes in the histomorphometric (static) parameters between pre-surgery and 4 weeks after surgery and those between 4 weeks and 12 weeks after surgery were assessed by the t-test while changes in the circulating parameters of bone metabolism were analyzed by Friedman's test. RESULTS: Bone formation parameters including carboxy terminal propeptide of human type I procollagen (PICP), alkaline phosphatase (ALP) and intact osteocalcin (i-OC) were all extremely high before surgery. These parameters initially increased after PTX-AG and thereafter gradually declined. In contrast, the circulating bone resorption parameters including tartrate-resistant acid phosphatase (TRAP) and deoxypyridinoline (Dpyr) were also extremely high at baseline but markedly declined after operation. Osteoid-related parameters including osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th) all initially increased at 4 weeks after PTX-AG. In contrast, osteoblast surface (Ob.S/BS), osteoclast surface (Oc.S/BS), eroded surface (ES/BS), and fibrosis volume (Fb.V/TV) all decreased at 4 weeks after surgery, while Ob.S/BS decreased further at 12 weeks in cases 1-6. Although bone mineralization was ongoing at 4 weeks after surgery, both the mineral apposition rate (MAR) and bone formation rate (BFR) remained below the mean for normal individuals. CONCLUSIONS: The circulating bone formation parameters and osteoid-related parameters showed an initial increase after PTX-AG. The concomitant decline in the circulating bone resorption parameters reflected the reduction in bone resorption. BFR decreased, but bone mineralization did not stop after PTX-AG.

Acid Phosphatase↗

PubMed2003

Treatment of tibial defect and bone nonunion with limb shortening with external fixator and reconstituted bone xenograft.

OBJECTIVE: To explore the effect of external fixator and reconstituted bone xenograft (RBX) in the treatment of tibial bone defect, tibial bone nonunion and congenital pseudarthrosis of the tibia with limb shortening. METHODS: Twenty patients (13 males and 7 females) with tibial bone defect, tibial bone nonunion or congenital pseudarthrosis of the tibia with limb shortening were treated with external fixation. Two kinds of external fixators were used: a half ring sulcated external fixator used in 13 patients and a combined external fixator in 7 patients. Foot-drop was corrected at the same time with external fixation in 4 patients. The shortened length of the tibia was in the range of 2-9 cm, with an average of 4.8 cm. For bone grafting, RBX was used in 12 patients, autogenous ilium was used in 3 patients and autogenous fibula was implanted as a bone plug into the medullary canal in 1 case, and no bone graft was used in 4 patients. RESULTS: All the 20 patients were followed-up for 8 months to 7 years, averaging 51 months. Satisfactory function of the affected extremities was obtained. All the shortened extremities were lengthened to the expected length. For all the lengthening area and the fracture sites, bone union was obtained at the last. The average healing time of 12 patients treated with RBX was 4.8 months. CONCLUSIONS: Both the half ring sulcated external fixator and the combined external fixator have the advantages of small trauma, simple operation, elastic fixation without stress shielding and non-limitation from local soft tissue conditions, and there is satisfactory functional recovery of affected extremities in the treatment of tibial bone defects, tibial bone nonunion and congenital pseudarthrosis of the tibia combined with limb shortening. RBX has good biocompatibility and does not cause immunological rejections. It can also be safely used in treatment of bone nonunion and has reliable effect to promote bone healing.

Adolescent↗

PubMedDate not supplied

Recovery of stromal stem cells in bone sarcoma patients after chemotherapy: implication for cell-based therapy in bone defect reconstruction.

Bone sarcomas, such as osteosarcoma (OS) or Ewing sarcoma (ES), frequently arise in the intramedullary region of long bones. Patients affected by bone sarcomas are treated with preoperative aggressive chemotherapy immediately after diagnosis. After chemotherapy, patients undergo surgery that frequently entails the excision of wide bone segments. If a large segment of the bone is lost (defined as a critical defect) the patient undergoes bone reconstruction. Because bone marrow derived stromal stem cells (SSC) offer great promise for cell-based regenerative medicine in bone reconstruction, we investigated whether SSC could be isolated from chemotherapy-treated bone sarcoma patients. We also investigated whether chemotherapy modified SSC differentiation capability. We studied 9 SSC derived from OS and ES patients that had undergone chemotherapy and 5 SSC derived from bone sarcoma patients that had not undergone chemotherapy. SSC could be obtained from all the patients analyzed regardless of whether the patients received chemotherapy or not. Our results also showed that post-chemotherapy SSC can be cultured and expanded ex vivo, these cells retained the ability to differentiate toward the osteogenic lineage in vitro. In conclusion, our results support that SSC cells can be obtained from bone sarcoma patients that undergo chemotherapy and suggest that SSC can be used for cell-based bone reconstruction techniques in bone sarcoma patients treated with preoperative chemotherapy.

Adolescent↗

PubMed1992

[The biological fixation strength of the bone particle impregnated bone cement].

This article reports the result of the comparative study on the biological fixation strength of two kinds of bone particle impregnated bone cement. Organic and inorganic bone particle impregnated bone cement were implanted into alternative side of the upper femurs of New Zealand rabbits. The cancellous bone and cortical bone segments of the implanted femurs removed at intervals of 1, 2 and 3 months after operation were subjected to push-out test. In cancellous bone segment, shearing strength of cement-bone interface was increased gradually, but no significant difference between these two kinds of cement after 3 months operation. In cortical bone segment, the interface shearing strength was lower than that of the cancellous bone, but it increased rapidly from 1 month, especially for the organic bone particle bone cement, after 3 months operation the interface shearing strength had a significant difference between the two kinds of cement. More prominent biological fixation effect showed in the organic bone particle group.

Animals↗

PubMed2005

[Promoting effects of serum-free murine bone marrow endothelial cell conditioned medium on the growth of bone marrow endothelial cells].

To study the effects of serum-free murine bone marrow endothelial cell conditioned medium (mBMEC-CM) on the growth of bone marrow endothelial cells, mBMEC-CM was collected and ultrafiltrated by Centriprep-10. The retentate of mBMEC-CM [molecular weight (MW)>10 kDa] and the filtrate of mBMEC-CM (MW<10 kDa) were obtained. The effect of bone marrow conditioned media, their components and exogenous cytokines on the formation of endothelial cell colonies were observed. The effect of bone marrow conditioned media, their components and exogenous cytokines on the proliferation of murine bone marrow endothelial cells were determined by [(3)H]-thymidine incorporation. The method of hybridizing to the Atlas cDNA array was used to determine the expression of cytokine mRNAs in bone marrow endothelial cells. The results obtained are as follows: vWF was expressed in bone marrow endothelial cells. The original mBMEC-CM and MW>10 kDa component of mBMEC-CM promoted the proliferation of bone marrow endothelial cell colonies and increased [(3)H]-thymidine incorporation of bone marrow endothelial cells. The MW<10 kDa component did not affect the production of endothelial cell colonies and did not increase [(3)H]-thymidine incorporation of endothelial cells. Six cytokines (IL-6, IL-11, SCF, GM-CSF, VEGF, bFGF) promoted the proliferation of bone marrow endothelial cell colonies. VEGF, bFGF and SCF increased [(3)H]-thymidine incorporation of bone marrow endothelial cells. According to the results of the Atlas cDNA array, GM-CSF,TGF-beta,BMP-2, bFGF, SCF, endothelin-2, thymosin beta10, MSP-1, connective tissue GF, PDGF-A chain, MIP-2 alpha, PlGF, neutrophil activating protein ENA-78, INF-gamma, IL-1, IL-6, IL-13, IL-11, inhibin-alpha mRNAs were expressed in endothelial cells. These results suggest that murine bone marrow endothelial cell conditioned medium promotes the proliferation of bone marrow endothelial cells.

Animals↗

PubMed1997

Tumor necrosis factor enhances parathyroid hormone-related protein-induced hypercalcemia and bone resorption without inhibiting bone formation in vivo.

Humoral hypercalcemia of malignancy results from the effects of tumor-produced factors on bone, kidney, and intestine that disrupt normal calcium homeostasis. Although parathyroid hormone-related protein (PTHrP) is a major mediator of the syndrome, tumors also produce other hypercalcemic factors, such as tumor necrosis factor (TNF), which may modulate the effects of PTHrP. It has been postulated that TNF may counteract the stimulatory effects of PTHrP on bone formation. To examine the effects of TNF on PTHrP-induced changes in calcium and bone metabolism, a murine tumor model of hypercalcemia was used. Nude mice were inoculated with Chinese hamster ovarian (CHO) cells expressing human TNF (CHO/TNF) or nontransfected CHO cells (CHO/-) and further treated with injections of human PTHrP(1-34) or vehicle. The effects of TNF, PTHrP, and the combination of the two factors on blood ionized calcium, osteoclast recruitment, and bone histomorphometry were evaluated. Mice bearing CHO/TNF tumors that were injected with PTHrP had significantly higher calcium concentrations, increased committed osteoclast progenitors, and mature osteoclasts as well as enhanced bone resorption compared with mice bearing CHO/TNF tumors injected with vehicle or those bearing CHO/- tumors injected with PTHrP or vehicle. A 2-fold increase in new woven bone formed in the calvaria at sites of previous bone resorption was observed in CHO/TNF mice treated with PTHrP. Bone formation rates in the vertebrae were similar in both CHO/- and CHO/TNF mice treated with PTHrP. These data demonstrate that the hypercalcemic effects of PTHrP are enhanced by TNF and that this effect is due to the increased production of committed osteoclast precursors with a subsequent increase in osteoclastic bone resorption. Furthermore, PTHrP caused a coupled increase in osteoclastic bone resorption and new bone formation that was not inhibited by TNF. These findings highlight the complex interactions that may occur between tumor-produced factors on bone that result in malignancy-associated hypercalcemia and suggest that TNF may not be responsible for the decreased bone formation seen in some patients with this condition.

Animals↗

PubMed2006

Ectopic bone induction by equine bone protein extract.

Demineralized bone matrix from horse has been reported to be osteoinductive. However, its performance was inferior to autogenous bone graft in terms of new bone formation. In the present experiment, an equine bone protein extract-COLLOSS E was investigated for its osteoinductivity in a rat model. At the mean time, carboxymethyl-cellulose (CMC) was tested as a potential carrier for the protein extract. 18 male Wistar rats (8 weeks) were employed in the experiment. Each rat was implanted randomly with the 2 of the following implants, one on each side of the abdominal muscle. 1) COLLOSS E lyophilisate. 2) PEEK ring holder. 3) 3% or 10% CMC .in gel or lyophilized form 4) COLLOSS E lyophilisate with 3% CMC, implanted as gel or in lyophilized form. 5) COLLOSS E suspension with 10% CMC, implanted as gel or in lyophilized form. The rats were followed up for 21 days. After termination, samples were subjected to macroscopic examination, plain radiograph, micro-CT and histological evaluations. The results showed that PEEK ring or CMC alone could not induce ectopic bone formation. COLLOSS E lyophilisate has a slightly higher (6 out of 7) positive bone formation rate over COLLOSS E/3% CMC (3 out of 5, both gel and lyophilized form), however, the difference is non-significant (p=0.36, Fisher's exact test). 10% CMC with COLLOSS E did not show ectopic bone formation when implanted as gel form (0/8), while 1 positive bone formation was found when implanted as the lyophilized form (1/4). Bone tissue volume ranged from 0 mm(3) to 23.1mm(3) for COLLOSS-E lyophilisate alone and 0 to 29.7mm(3) for COLLOSS E/3%CMC (gel or lyophilized form). We concluded that equine bone protein extract has the ability to induce ectopic bone formation in the rat model. CMC could be a potential carrier, however, further studies are needed to verify the proportion and efficacy.

Animals↗

PubMed2006

[Clinical experience with bone morphogenetic protein 7 (BMP 7) in nonunions of long bones].

BACKGROUND: Nonunions of long bone fractures are considerable therapeutic and economic problems with increasing tendency. Basic surgical options are autogenous cancellous bone grafting, rod dynamization, reamed nailing, plate fixation with compression, and bone transport techniques. If these methods fail to work, alternative treatment options are needed. MATERIAL AND METHODS: Since May 2001 treatment with recombinant human (rh) bone morphogenic protein 7 [BMP-7 or osteogenic protein 1 (OP-1)] in combination with a type one collagen carrier has gained interest. BMP 7 induces the formation of new bone by differentiation of stem cells, thereby initiating the reaction cascade of osteogenesis. Nonunions over 9 months and unsuccessful bone grafting delineate the indication. RESULTS: We report our experience with 21 patients and nonunion of long bone fractures. Between July 2002 and June 2004, 23 units of BMP 7 were implanted. The implantation sites were 7 femora, 12 tibias, 2 humeri, and 2 forearms. In ten cases BMP 7 was combined with a new osteosynthesis and bone grafting and in five patients with bone grafting alone. In contrast in eight patients BMP 7 was applied as a single procedure without any bone grafting or any change of the osteosynthesis. CONCLUSION: There were no peri- or postoperative complications. Follow-up was obtained for a minimum of 6 months. Of 23 implantations, 22 were successful with bony healing revealed by clinical and radiological evaluation. In one patient no bony consolidation of the nonunion has been seen so far. In summary, based on our results we propose BMP 7 as an additional innovative therapy of long bone nonunions.

Adult↗

PubMed2006

Changes in the serum sex steroids, IL-7 and RANKL-OPG system after bone marrow transplantation: influences on bone and mineral metabolism.

This study prospectively investigated the changes of the serum levels of the sex steroids, IL-7, soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT) recipients. This study also examined whether the changes of these cytokine levels and sex steroids actually influence bone turnover and post-BMT bone loss by correlation analysis. Data were analyzed from 39 patients (33.6+/-6.4 years, 19 men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The bone turnover markers, sex steroids and the cytokine levels were measured before BMT and serially after BMT. The mean bone loss in the lumbar spine and the total proximal femur was 5.9% (P < 0.01) and 11.3% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas the bone resorption increased. For the female recipients, the estradiol levels declined at 1 week after BMT, and they did not recover to the basal levels. For the male recipients, the testosterone levels decreased at 1 week and then it increased to its baseline level. The IL-7 levels reached their maximum at 1 week and then declined to baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio showed their peak at post-BMT 3 weeks. The mean daily dose of steroid was associated with suppressed bone formation, enhanced bone resorption and increased sRANKL levels. The IL-7 levels were also noted to be either positively correlated with the levels of ICTP or they were negatively correlated with the levels of osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the proximal femur was influenced by the decreased sex steroids and increased IL-7 levels. During the observation period, the IL-7 levels showed positive correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female patients, the serum IL-7 levels were negatively associated with the estradiol levels at 1 and 3 weeks after BMT. All these findings suggest that IL-7 plays an important role for post-BMT bone loss, and this possibly happens via the RANKL pathway. These data also suggest that the up-regulation of IL-7 during the early post-BMT period may result from a deficiency of estrogen.

Adult↗

PubMed2004

Bone reconstruction of large defects using bone marrow derived autologous stem cells.

Bone is a tissue that has the ability to heal itself when fractured. Occasionally, a critical defect can be formed when part of the bone is lost or excised, in this case the bone fails to heal and requires bone reconstruction to prevent a non-union defect. Autogenous cancellous bone is the current gold standard treatment in bone loss. Because the amount of autogenous cancellous bone that can be harvested is limited, the expanding need for bone reconstruction is paired by the growth of interest in the discipline of tissue engineering. Labs worldwide are working to provide the right carrier and the right set of cells that, once retransplanted, will ensure bone repair. Several investigators have focused their attention on a subset of autologous non-hematopoietic stem/progenitor cells contained in the adult bone marrow stroma, referred to as stromal stem cells (SSC), as the appropriate cells to be transplanted. The use of autologous cells is facilitated by less stringent ethical and regulatory issues and does not require the patient to be immunologically suppressed. In pre-clinical and clinical protocols of critical defects in which SSC are employed, two approaches are mainly used: in the first, SSC are derived from bone marrow and directly introduced at the lesion site, in the second, SSC are derived from several sites and are expanded ex vivo before being implanted. Both approaches, equally correct in principle, will have to demonstrate, with definitive evidence of their efficacy, their capability of solving a critical clinical problem such as non-union. In this report we outline the difficulties of working with SSC.

Bone Marrow↗

PubMed2005

Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues.

Diabetic osteoporosis is increasingly recognized as a significant comorbidity of type 1 diabetes mellitus. In contrast, type 2 diabetes mellitus is more commonly associated with modest increases in bone mineral density for age. Despite this dichotomy, clinical, in vivo, and in vitro data uniformly support the concept that new bone formation as well as bone microarchitectural integrity are altered in the diabetic state, leading to an increased risk for fragility fracture and inadequate bone regeneration following injury. In this review, we examine the contribution that insulin, as a potential anabolic agent in bone, may make to the pathophysiology of diabetic bone disease. Specifically, we have assimilated human and animal data examining the effects of endogenous insulin production, exogenous insulin administration, insulin sensitivity, and insulin signaling on bone. In so doing, we present evidence that insulin, acting as an anabolic agent in bone, can preserve and increase bone density and bone strength, presumably through direct and/or indirect effects on bone formation.

Animals↗

PubMed2003

Receptor activator of NF-[kappa]B ligand arrests bone growth and promotes cortical bone resorption in growing rats.

Receptor activator of NF-kappaB ligand (RANKL), produced by osteoblastic lineage cells and activated T cells, is an essential factor for osteoclast differentiation, activation, and survival. Therefore, RANKL is a focal point of therapies targeting bone diseases where there is an imbalance of bone metabolism in favor of bone resorption. The present study assesses the effects of exogenous RANKL on growing bone. RANKL (100 microg x kg-1x day-1 for 7 days) administered to Sprague-Dawley weanling rats caused major deficits in growth, appearance, and bone mineral densities (BMD). Urinary deoxypyridinoline crosslinks, a measure of bone turnover, were higher in the RANKL-treated rats (P = 0.031), and the bone mineral content was lower (P < 0.001). The final BMD in the RANKL-treated rats was lower (P = 0.039) than in the control rats (19 +/- 7 vs. 38 +/- 5 mg/cm3). Moreover, calculated cortical bone density in each bone slice (total BMD - trabecular BMD) indicated there was only 5% cortical bone remaining in RANKL-treated rats. We conclude that therapies targeting RANKL are likely to have effects on cortical as well as trabecular bone density.

Amino Acids↗

PubMed1990

A theoretical model of endochondral ossification and bone architectural construction in long bone ontogeny.

The role of mechanical stresses in the formation of endochondral ossification patterns and the construction of basic bone architecture in human long bones is investigated using a three-dimensional generalized model of long bone development. The distribution of mechanical stress which is created in developing bones as a result of intermittent mechanical loading is calculated using a computer model that mathematically represents the bone's geometry, material properties and loading conditions. The process of endochondral ossification is simulated by iteratively converting cartilaginous regions of the computer model to bone, based on the calculated intermittent hydrostatic and shear stress distributions. Once local regions of mineralized bone have formed, these regions are remodeled according to an algorithm which relates bone density to a mechanical stress stimulus. The results simulated the correct sequence of the appearance of morphological structures which are common to long bones in the human appendicular skeleton. These developmental structures include the site of the first endochondral bone and the secondary ossification center and the tubular nature of long bones. Our results suggest that mechanical loading histories may influence bone morphogenesis beginning from the early stages of endochondral ossification and continuing throughout life. The stress-based algorithms may be part of the 'rules of construction' or 'developmental constraints' which guide limb ontogeny.

Algorithms↗

PubMed1992

Long-term effect of orchidectomy on cortical bone from rat femur: bone mass and mechanical properties.

The study comprised seven groups of intact rats killed at 9, 12, 15, and 24 months of age, and three groups of rats castrated at the age of 9 months and killed together with the intact rats 3, 6, and 15 months after castration. The composition, dimension, and mechanical properties of intact bone as well as the constituent bone collagen from femoral diaphyses were investigated in relation to both age (9-24 months) and castration. Castration had no effect on density and only minor effect on ash and collagen contents. An age-related increase in bone mass, cross-sectional area, and wall thickness of the diaphyses was arrested (bone mass, area) or even reversed (to a decrease in wall thickness) after castration. Therefore, a growing difference, pronounced from 6 months after castration, between intact and castrated rats was observed in bone mass, cross-sectional area, and wall thickness. The compressive mechanical strength of intact bone normalized with regard to cross-sectional area was unaffected by castration, whereas castration tended to increase the stiffness of the bone collagen. When observed in a polarization microscope, two different zones in cross sections of the diaphyses were apparent. The average diameter of the border line separating the two zones was independent of age and castration. By measuring the average thickness of each of the two zones, age-related periosteal bone formation and endosteal bone resorption were demonstrated. After castration, the rate of bone formation was reduced and the rate of bone resorption was accelerated. Castration was thus found to affect the composition and the quality of the cortical bone to a minor extent only.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1982

The use of decalcified granulated homologous cortical bone matrix in the correction of diaphyseal bone defect. An experimental study in rabbits.

In order to investigate an alternative way to correct diaphysial bone defects, granulated decalcified homologous cortical bone was used as a graft. Because of the suitable anatomic arrangement, the forearm of rabbits was chosen as an experimental model of bone defect. A 2 cm long bone cylinder was removed from the diaphysis of both radii preserving the periosteum. The artificial bone defect was filled with granular decalcified bone on the right side. The left side was used as control and kept empty or filled with undecalcified granular bone. The 18 animals were sacrificed in batches, 3,6, and 9 weeks after the operation. New bone formation was followed by X-rays, routine histology and incorporation of calcein blue, xylenol orange and tetracycline. In the decalcified granular bone grafts new bone formation was already detected at the first week and 9 weeks after the graft operation there was a well developed cylindric ossicle, in 89% of the cases. In some cases a medullary canal was present. No bone formation was found neither in the empty defects nor in the ones filled with undecalcified granular bone grafts.

Animals↗

PubMed1976

Bone resorption measurement with unusual bone markers: critical evaluation of the method in phosphorus-deficient and calcium-deficient growing rats.

An in vivo method to evaluate bone resorption in rats, by using unusual bone seekers not dependent on renal tubular transfer, is described and a critical evaluation of the method is made. In our experimental conditions, 85Sr and 177Lu are virtually exclusively localized in bone whereas 237Np remains unchanged in different soft organs, so that the concomitant use of these markers can be used for measuring bone resorption. If osteolysis occurs 21 days after the injection of these markers, under our experimental conditions, any increase in the urinary excretion of 177Lu and 237Np represents a rise in bone resorption, whereas an increase in Sr excretion reflects both and renal tubular events. According to our bone localization studies, the enhancement of Lu and Np excretion reflects primarily an increase in cortical bone resorption localized at the endosteal (Lu) and at the periosteal (Np) surfaces respectively. In addition, strontium is considered to be the marker of mineral resorption whereas Lu and Np, under our experimental conditions, would reflect the organic bone resorption. This method is tested in phosphorus-deficient rats and in calcium-deficient rats which exhibit disturbances of calcium metabolism at both the bone and kidney levels. In agreement with previous investigations, the use of these bone markers to evaluate osteolysis shows: (a) after a 1-week phosphorus deficiency, a slight increase in cortical bone resorption with a simultaneous fall in calcium and strontium renal tubular reabsorption, and (b) after a 1-week calcium deficiency, a high rise in cortical bone resorption with a simultaneous increase in the renal tubular reabsorption of calcium and strontium.

Animals↗

PubMed1999

Changes in bone mass and bone turnover following ankle fracture.

Bone loss and increased bone turnover are recognized local changes after a fracture, but the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following ankle fracture. Fourteen subjects (7 postmenopausal women and 7 men, mean age 63 years) were recruited following fracture of the distal tibia and fibula. Bone mineral density (BMD) of the ankle and proximal femur were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the calcaneus at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and QUS. There was a significant decrease in BMD at the ultradistal ankle (p<0.001), the trochanteric region of the hip (p<0.01) and QUS of the heel after ankle fracture. This bone loss was maximal for ultradistal ankle BMD by 6 weeks at 13% (p<0.001) and for the trochanter by 26 weeks at 3% (p<0.01). The ankle BMD returned to baseline at 52 weeks but the trochanter BMD did not. Velocity of sound (VOS) decreased at 6 weeks by 2% (p<0.01) and broadband ultrasound attenuation (BUA) by 15% (p<0.01). VOS recovered completely by 52 weeks, but BUA did not return to baseline. Bone formation markers increased significantly between 1 and 4 weeks by 11-78% (p<0.01), and iBAP returned to baseline at 52 weeks but PINP and Oc remained elevated. Bone resorption markers did not increase and NTx was decreased at 52 weeks. We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Ankle BMD and heel VOS recovered at 52 weeks (trochanteric BMD and heel BUA did not) and the bone turnover markers returned toward baseline.

Absorptiometry, Photon↗