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PubMed2006

[Tibial bone harvesting technique for filling maxillary bone gaps in implantology].

We present an easy and quick technique of tibial bone grafting that can be used in maxillary bone losses, specially in implantology. The surgical technique is performed under general anaesthesia. A 1.5 cm skin incision is made on the anteromedial side of the tibia. Then the bone marrow can be approached through a cortical window drilled with a motorized trephine. At this stage, a disposable bone aspirator is used to collect the cancellous bone. At the end of the procedure, the periosteum, the subcutaneous tissues and the skin are sutured in three layers. The quantity of harvested cancellous bone varies from 18 to 30 cc. The procedure duration is about twenty minutes. The complication rate is low and the patients are able to walk a few hours after the procedure. They leave the hospital on the day after. Tibial bone harvesting is an alternative technique that can be chosen in cases with large bone defects. This tibial graft can be recommended because of its low morbidity, the quality of the bone and the short time duration of the procedure. Some details must be pointed out. A medial tibial surgical approach is for us better than a lateral approach because of its lower morbidity and because the bone is more superficial. The use of a motorized trephine is important to lift precisely the cortical bone window and because it is less traumatic than the hand trephine. The disposable bone aspirator is an excellent option to pick-up bone marrow with a minimum loss of bone material and in a shorter time.

Bone Marrow Transplantation↗
PubMed2001

Use of markers of bone turnover for monitoring bone metastases and the response to therapy.

Metastatic bone disease is a frequent complication of breast and other cancers, resulting in skeletal complications that are a significant cause of morbidity and mortality. Bone metastases can be difficult to diagnose radiologically and it can also be difficult to evaluate patients' response to treatment by using the methods that are currently available (radiography, bone scans, and computed axial tomography scans). These are relatively insensitive procedures, thus, there is a requirement for new methods for assessing bone response to ensure patients benefit from the optimum type and duration of treatment. Biochemical markers of bone turnover, such as N-telopeptide and the pyridinium cross-links pyridinoline and deoxypyridinoline, may provide information on bone dynamics that in turn may reflect disease activity in bone. Several studies have shown bone markers to be elevated in cancer patients who have documented evidence of metastatic bone disease. Increased levels are also observed in some patients without clinical evidence of bone metastases, when compared with normal subjects. Rises in such markers may be the first indication of bone involvement and therefore may potentially be useful in early diagnosis of progression. Preliminary data suggest bone marker level correlates with the extent of metastatic disease and the number of skeletal sites involved. Markers of bone turnover may be helpful in identifying those patients likely to respond to bisphosphonate treatment. Such markers are also potentially useful in monitoring the effectiveness of bisphosphonate therapy in the management of bone metastases, in both patients with metastatic breast disease and multiple myeloma.

Amino Acids↗
PubMed2003

Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys.

Using a clinically relevant regimen, this study investigated the effects of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on bone loss, biochemical markers of bone turnover, densitometry, histomorphometry, biomechanical properties, and bone concentration in aged ovariectomized monkeys. Sixty-six female cynomolgus monkeys, aged 9 years and older, were ovariectomized (OVX) or sham operated. Intravenous (iv) bolus injections of ibandronate at 10, 30, or 150 microg/kg or placebo were administered at 30-day intervals (corresponding to intervals of 3 months in humans), starting at OVX, for 16 months. OVX significantly decreased bone mass at the lumbar spine, proximal femur, femoral neck, and radius and increased bone turnover in a time-dependent manner, as assessed by dual energy X-ray absorptiometry, peripheral quantitative computed tomography, or histomorphometry. Ibandronate iv bolus injections administered at 30 microg/kg every 30 days prevented osteopenia induced by estrogen depletion. OVX-induced increases in bone turnover (as determined by activation frequency, bone formation rate, and biochemical markers of bone turnover, including urinary N-telopeptide and deoxypyridinoline excretion and serum values for osteocalcin and bone-specific alkaline phosphatase) were suppressed on treatment, and bone mass, architecture, and strength were preserved at clinically relevant sites. Treatment with high-dose (150 microg/kg/dose) iv bolus injections of ibandronate further increased bone mass and improved bone strength at both the spine and femoral neck, without adversely affecting bone quality. In contrast, treatment with a 10 microg/kg/dose only partially prevented the OVX-induced effects. These data support the potential for the long-term administration of ibandronate by intermittent iv bolus injections in humans to prevent osteoporosis and improve bone quality at clinically relevant sites.

Animals↗
PubMed1998

Production of interleukin-11 in bone-derived endothelial cells and its role in the formation of osteolytic bone metastasis.

The interactions of the cells in the bone microenvironment play important roles in bone remodeling. Osteoblasts are involved in the bone remodeling through the production of soluble factors that regulate proliferation and differentiation of osteoclasts and through cell-cell interactions. Histological studies have suggested that endothelial cells are also associated with some osteolytic bone diseases. However, it is still unclear how endothelial cells contribute to bone resorption. We established bone-derived endothelial cells (BDECs) to study their roles in bone remodeling. The established BDECs promoted bone resorption in a murine neonatal calvaria organ culture system by secreting a soluble bone resorption-inducing factor(s) when stimulated by several inflammatory cytokines. This bone resorption-inducing factor was identified as interleukin-11 (IL-11). IL-11 is known to enhance bone resorption by promoting osteoclastogenesis and by suppressing the activity of osteoblasts. The production of IL-11 in BDECs was also promoted by conditioned medium of human melanoma A375M cells. Because A375M cells formed osteolytic bone metastasis in vivo, BDECs might be involved in pathological osteolysis by producing IL-11. These results suggest that endothelial cells in bone play important roles in the promotion of bone resorption by secreting IL-11 in physiological and pathological conditions.

Animals↗
PubMed2002

The comparative values of bone marrow aspirate and trephine for obtaining bone scan-targeted metastases from hormone-refractory prostate cancer.

Samples of metastatic prostate cancer to bone are difficult to obtain. The aim of this study was to compare the results of bone marrow aspirate and trephine biopsy for obtaining metastatic hormone-refractory prostate cancer (HRPC) samples using previous diagnostic planar 99(m)Tc-HDP bone scans to guide the procedure. All samples taken were for the purposes of research and molecular studies on HRPC. Twenty patients with HRPC had bone marrow aspirate and trephines taken from lesions in the posterior superior iliac spine or sacro-iliac region when shown on diagnostic 99(m)Tc-HDP bone scans. Three patients also underwent plain X-ray, 18F-positron emission tomography bone scan, pelvic MRI scan and 99(m)Tc nanocolloid bone marrow scans. These images were used to assess if the extra imaging information provided, such as three-dimensional localisation of the bone metastases, was of value for target bone metastases. Cancer cells were obtained in 15/20 (75%) cases in which a trephine biopsy was attempted and 0/20 of cases in which a bone marrow aspiration was attempted. The additional information provided by the range of other imaging investigations was of little benefit in obtaining tumour samples, but did suggest why negative biopsies were obtained in some cases after targeting with planar bone scans. We recommend the use of bone marrow trephine biopsy alone, guided by previous diagnostic 99(m)Tc planar bone scan as a practical method to obtain prostate cancer cells from bone metastases.

Aged↗
PubMed2000

Parathyroidectomy for primary hyperparathyroidism induces positive uncoupling and increases bone mineral density in cancellous bones.

OBJECTIVE: Osteopenia is an important feature of primary hyperparathyroidism (PHP). However, little is known about the change of bone mineral density (BMD) in PHP after surgery. The aim was to investigate the mechanisms of increased BMD after parathyroidectomy in patients with PHP. DESIGN: Prospective observational study. PATIENTS: Ten patients with PHP (7 women, 3 men; mean age 53.2+/-9.1 years). All patients underwent parathyroidectomy for excision of parathyroid adenoma. MEASUREMENTS: BMDs of two cancellous bone-rich sites (L2-L4 lumbar spine and ultra-distal end of the radius, RUD) and one cortical bone-rich site (distal third of the radius, R33%) were measured using dual energy X-ray absorptiometry, before, and 3, 6 and 12 months after surgery. Serum intact PTH, intact osteocalcin, bone type alkaline phosphatase (b-ALP), alkaline phosphatase, calcium, and urinary deoxypyridinoline (Dpd) were measured before, and 1 and 3 days, and 1, 2, 3, 4, 6, 8, 12, and 24 weeks after surgery. RESULTS: Parathyroidectomy resulted in a significant increase in BMDs of L2-L4 and RUD at 3 months postoperatively. Urinary Dpd levels decreased within a few days after surgery, while b-ALP and osteocalcin decreased more slowly throughout the first few months after surgery. The ratio of osteocalcin/Dpd at 1 week after surgery correlated significantly with the percentage change in BMD of L2-L4 at 3 and 6 months after surgery. The ratio of osteocalcin/Dpd at 2 weeks correlated significantly with the percentage change in BMD of L2-L4 at 3, 6 and 12 months after surgery. The preoperative values of osteocalcin, b-ALP, PTH and calcium were positively correlated with the change in BMD of RUD at 3 months and L2-L4 at 12 months, RUD at 6 months, RUD at 3 months and L2-L4 at 12 months, respectively. CONCLUSIONS: In primary hyperparathyroidism patients, the major increase in bone mineral density following parathyroidectomy occurs within 3 months. Parathyroidectomy resulted in a marked increase in bone mineral density of cancellous bones compared to that of cortical bones. The early increase in bone mineral density was due to a preferential activation of bone formation over bone resorption as evidenced by changes in bone metabolic markers. Our results also showed that the preoperative levels of bone metabolic markers may predict the gain in bone mineral density after parathyroidectomy.

Adenoma↗
PubMed2002

Bone histology and bone mineral density after correction of acidosis in distal renal tubular acidosis.

BACKGROUND: The association between chronic metabolic acidosis and alterations in bone cell functions has been demonstrated in vitro and in animal studies. However, the causal role of acidosis and the effects of alkaline therapy on bone histology and bone mineral density in chronic metabolic acidosis have never been systematically demonstrated in humans. This study was conducted to examine the alterations in bone mineral density and bone histology before and after correction of acidosis among patients with distal renal tubular acidosis (dRTA) METHODS: Correction of metabolic acidosis by potassium citrate was done in non-azotemic dRTA patients, 6 females and 4 males, who had never received long-term alkaline therapy before enrolling into this study. Blood chemistries, serum intact parathyroid hormone, and 24-hour urine collection for the determination of urinary calcium, phosphate, sodium, potassium, bone mineral density determination, and transiliac bone biopsy were done in all patients at baseline and after one year of potassium citrate therapy. RESULTS: Significant elevations in serum bicarbonate (16.5 +/- 3.0 vs. 24.6 +/- 2.8 mEq/L, P < 0.05) and urinary potassium excretion (35.2 +/- 7.9 vs. 55.4 +/-3.5 mEq/L, P < 0.05) were observed after potassium citrate therapy. No significant alterations in other serum and urine electrolytes were found after the therapy. Serum intact parathyroid hormone level was also significantly elevated after one year of treatment (12.8 +/- 7.3 vs. 26.2 +/- 8.7 pg/mL, P < 0.05). Bone formation rate was significantly suppressed at baseline and was normalized by the treatment (0.02 +/- 0.02 vs. 0.06 +/- 0.03 microm(3)/microm(2)/day, P < 0.05). There were non-significant elevations in trabecular bone volume, osteoblastic and osteoclastic numbers. Bone mineral densities in dRTA patients were also significantly decreased below normal values in most studied areas at baseline and were significantly elevated at the trochanter of femur (0.677 +/- 0.136 vs. 0.748 +/- 0.144 g/c m(2), P < 0.05) and total femur (0.898 +/- 0.166 vs. 0.976 +/- 0.154 g/c m(2), P < 0.05) after the treatment. CONCLUSIONS: This study demonstrates that alkaline therapy corrects abnormal bone cell function and elevates bone mineral density in dRTA patients, indicating the causal role of acidosis in the alterations of bone cell functions and reduction in bone mineral density. Parathyroid gland activity also may be involved in the adaptation of the body to chronic metabolic acidosis.

Acidosis, Renal Tubular↗
PubMed2002

Transmission of bone strain in the craniofacial bones of edentulous human skulls upon dental implant loading.

STATEMENT OF PROBLEM: Little is known about how craniofacial bones that are distant from dental implants are loaded. Whether bone experiences different strain when implants of different diameters are loaded is unknown. PURPOSE: This study was designed to (1) characterize bone strain both adjacent to and distant from dental implants and (2) compare bone strain in response to the same loads on small-diameter and large-diameter implants. MATERIAL AND METHODS: On 4 edentulous, dry adult human skulls, the buccopalatal midpoint of the edentulous occlusal surface was marked unilaterally in the maxillary first molar area with a round bur. A hole for implant placement was prepared, and 2 self-tapping titanium implants (3.75 x 7 mm and 4 x 7 mm) were placed in the same location and at the same orientation, one after the other. A 4-mm-long titanium abutment was connected to the implant. Each implant was loaded 10 degrees lateral to its longitudinal axis, simulating a lateral occlusal force in 3 of the skulls. In skull 2, loading was along the longitudinal axis of the implant and simulated a vertical occlusal force. The magnitude of the ramp forces was 0 to 100 N. Uniaxial strain gages and/or 3-element strain rosettes were implanted in the supramolar cortical bone, the supraincisor cortical bone, the zygomaticomaxillary suture, and the zygomaticotemporal suture. All strain gages/rosettes were excited with 500 mV DC, and the output signals were recorded with a strain conditioner. Tensile strain was expressed as positive values and compressive strain as negative values. Student t tests were used to test for normal distribution of bone strain within each skull; Wilcoxon tests were applied for skewed distribution between small- and large-diameter implants and between 50-N and 100-N loads (P<or=.05). RESULTS: Bone strain both adjacent to and distant from the implants was complex: compressive strain in the buccal cortical bone superior to the implants; tensile strain in the ipsilateral supraincisor cortical bone but compressive strain in the contralateral supraincisor cortical bone; and tensile strain anterior to the zygomaticotemporal suture but compressive strain posterior to the suture. With the same applied loads, bone strain was higher for large-diameter implants than for small-diameter implants for all the above cortical locations (P<.01 to.001) except posterior to the zygomaticotemporal suture. CONCLUSION: Within the limitations of this study, bone strain resulting from dental implant loading was distributed to cortices not only adjacent to but also distant from dental implants. The large-diameter implant was more facilitative of stress transfer to cortical bone than the small-diameter implant tested.

Adult↗
PubMed1996

Bone regeneration with resorbable polymeric membranes: treatment of diaphyseal bone defects in the rabbit radius with poly(L-lactide) membrane. A pilot study.

Tubular poly(L-lactide) membranes with a pore size of 5-15 microns and a molecular weight of 70,000 Daltons were implanted into 24 New Zealand skeletally mature rabbits to cover 10-mm mid-diaphyseal defects of the radius of the forelimb. An identical defect on the contralateral limb was not treated with the membrane and served as a control. The animals were killed at 1, 2, 4, 8, 12, 24, 36, and 64 weeks after implantation, and radiographic and microscopic studies were conducted. The canals of the polymeric tubes were initially filled with blood. At 2 weeks, there was direct woven bone formation within the polymeric tube in continuity with the fragment cortices and its medullary canal. The formation of woven bone across the defect progressed until reconstruction of the defect had occurred at 6-8 weeks. The bone continued to remodel throughout the observation period of 64 weeks. By 12 weeks, bone within the lumen of the implant consisted of cancellous bone and cortical bone lining the membrane walls. At 24, 36, and 64 weeks, the implants were filled with cancellous bone and cortical bone in direct apposition to the polymer membrane. For one implant, the newly formed woven bone had only incompletely filled the defect at 8 weeks. This resulted in a nonunion with a residual gap of 0.5 mm and the appearance of mature bone. There was extensive bone formation along the intraosseous membrane in both control and implanted defects, although the untreated defects were rapidly filled with overlying muscle and soft tissues. The osseous activity of the untreated defects appeared confined to the bone ends by the interposed muscle and fibrous soft-tissue margins. The untreated defects resulted in radial-ulnar synostosis along the intraosseous membrane with cortical bone caps at the bone ends. The poly(L-lactide) membrane remained intact throughout the 64-week period without evidence of significant degradation. The membranes were encapsulated in a thin fibrous tissue. There was no histological evidence of acute or chronic inflammation associated with the implants.

Animals↗
PubMed2005

Recombinant human bone morphogenic protein-2-enhanced anterior spine fusion without bone encroachment into the spinal canal: a histomorphometric study in a thoracoscopically instrumented porcine model.

STUDY DESIGN: A thoracoscopically assisted 5-level anterior spinal fusion and instrumentation model analyzing new bone formation when using recombinant human bone morphogenic protein-2 (rhBMP-2) with a collagen hydroxyapatite-tricalcium phosphate (HA/TCP) composite sponge carrier. OBJECTIVE: To determine whether new bone formation extends beyond the posterior confines of the vertebral body encroaching into the spinal canal when rhBMP-2 is used to enhance anterior fusion. SUMMARY OF BACKGROUND DATA: A possible concern regarding the use of rhBMP-2 to enhance spinal fusion is the risk of unwanted bone formation leading to inadvertent fusion of adjacent levels or compression of neural elements. The safety of rhBMP-2 in one spinal application does not ensure similar results in other applications. Therefore, the expanded use of rhBMP-2 should occur only after carefully monitored preclinical and clinical studies for each new application. METHODS: Eighteen pigs underwent thoracoscopically-assisted instrumentation and fusion of 5 contiguous levels (T5-T10) and randomly assigned to 4 treatment groups: group 1 (n = 6): rh-BMP-2 on a HA/TCP-collagen sponge (Medtronic Sofamor Danek, Memphis, TN); group 2 (n = 4): iliac crest autograft; group 3 (n = 4): empty; group 4 (n = 4): HA/TCP-collagen sponge (Medtronic Sofamor Danek) only. In groups 1 and 4, the HA/TCP collagen sponge was morselized into small granules and pushed through a bone delivery funnel for implantation into the disc. At 4 months after surgery, spines were sectioned longitudinally through the midsagittal plane and underwent undecalcified processing. Bone formation extending beyond the margins of the original discectomy and the confines of vertebral body were evaluated histomorphometrically at each operative level. RESULTS: Recombinant human bone morphogenic protein-2 on a HA/TCP-collagen sponge induced significant new bone formation extending anterior to the confines of the vertebral body compared with the other treatment groups (P < 0.05). In addition, rhBMP-2 on a HA/TCP-collagen sponge induced significant new bone formation extending posterior to the original margins of the discectomy (P < 0.05). However, there was no new bone formation beyond the confines of the posterior vertebral body. The total bone volume in the rhBMP-2-HA/TCP-collagen sponge group was significantly greater compared with all other groups in both the discectomy fusion area and beyond the discectomy area (P < 0.05). CONCLUSIONS: Recombinant human bone morphogenic protein-2 on a HA/TCP-collagen sponge enhanced anterior spinal fusion and induced significant new bone formation extending beyond the margins of the original discectomy and anterior vertebral body, most likely secondary to migration of some morselized carrier fragments from the disc space. However, the new bone formation did not extend beyond the posterior confines of the vertebral body to encroach into the spinal canal because of the intact posterior anulus and/or posterior longitudinal ligament.

Animals↗
PubMed2004

Local biochemical markers of bone turnover: relationship to subsequent density of healing alveolar bone defects.

OBJECTIVES: This pilot study was designed to test whether biochemical markers of bone turnover in washes of periosteal or trabecular alveolar bone surfaces could be correlated with increases in bone density of an adjacent healing implant socket. METHODS: Ten subjects had a canula inserted into the alveolar crest and sterile phosphate-buffered saline was washed over the periosteal and trabecular surfaces and collected. Surgical flaps were reflected, 5 mm diameter bone cores were removed from the bone wash site, and standardized radiographs were taken. The sites were allowed to heal for 12 weeks, and radiographs were repeated. Bone washes of the healing sites were also collected after 2 and 12 weeks. Washes were analysed for bone turnover markers osteocalcin (OC; radioimmunoassay) and C-terminal telopeptide of Type 1 collagen (ICTP; enzyme-linked immunosorbent assay (ELISA)), and blood component albumin (ALB; ELISA). Changes in bone density during healing were determined by radiographic absorptiometry. RESULTS: OC/ALB and ICTP/ALB ratios were higher for trabecular than periosteal washes at baseline (p<or=0.01). Trabecular OC/ALB and ICTP/ALB were inversely correlated with increasing bone density of the healing bone core socket (r=-0.72, p=0.03; Pearson's correlation coefficient). CONCLUSIONS: Biochemical markers of bone turnover in bone washes of specific alveolar bone sites may prove helpful in predicting how the bone density will increase around healing dental implants.

Absorptiometry, Photon↗
PubMed1988

1,25-dihydroxyvitamin D3 corrects bone loss but suppresses bone remodeling in ovariohysterectomized beagle dogs.

The decrease in intestinal calcium absorption and lower blood levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D3] have been implicated in the pathogenesis of postmenopausal osteoporosis. This study evaluates the effects on bone of 1,25-(OH)2D3 therapy using the ovariohysterectomized dog model. The cessation of ovarian function was ascertained by an increase in serum LH levels 4 weeks after ovariohysterectomy, and significant bone loss was revealed four months after ovariohysterectomy. The bone loss was associated with an increase in the number of bone-forming cells and a decrease in the activity of these cells. The administration of 1,25-(OH)2D3 increased the activity of the bone cells and resulted in a reversal of all abnormalities in structural parameters of bone, including cancellous bone mass, trabecular wall thickness, trabecular plate separation, trabecular plate density, and trabecular plate thickness (which increased above normal). However, 1,25-(OH)2D3 therapy was also associated with a significant decrease in the number of bone-forming cells, resulting in lower bone formation at the tissue level. The results of this study indicate that 1,25-(OH)2D3 therapy can reverse the bone loss and osteoblastic insufficiency responsible for the maintenance of negative bone balance after the cessation of ovarian function. However, this therapy has a suppressive effect on bone cell number and bone turnover. This undesired side-effect of 1,25-(OH)2D3 therapy renders a chronic therapeutic regimen inefficient for the long term management of patients with osteoporosis. Intermittent 1,25-(OH)2D3 therapy or a sequential therapy using 1,25-(OH)2D3 along with substances known to increase the number of bone-forming cells is strongly suggested by these results.

Animals↗
PubMed2003

Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men.

Male osteoporosis is an increasingly important health problem. It is known that sex steroid hormones play an important role in regulating bone turnover and bone mass in males as well as in females. However, the exact mechanism of bone loss in men remains unknown. In the present study, 200 elderly men (age range, 55-85 yr) were followed for 4 yr to evaluate the relationships between hormone levels, bone turnover markers, bone mineral density, and rates of bone loss. Femoral and lumbar bone mineral density, bone ultrasound parameters at the os calcis, serum testosterone (T), serum estradiol (E(2)), SHBG levels, and bone turnover markers (urinary crosslaps and bone alkaline phosphatase) were evaluated for each man at enrollment and 4 yr afterward. The free androgen index (FAI) and free estrogen index (FEI) as well as measures of the bioavailable sex hormones [calculated bioavailable E(2) (c-bioE(2)) and T (c-bioT)] were calculated from total hormone levels and SHBG. In the total population, T, c-bioT, c-bioE(2), FAI, and FEI, but not E(2), decreased significantly with age, whereas SHBG increased significantly. Subjects with FEI, c-bioE(2), and E(2) levels below the median showed higher rates of bone loss at the lumbar spine and the femoral neck as well as higher speed-of-sounds decrease at the calcaneus with respect to men with FEI, c-bioE(2), and E(2) levels above the median. Serum bone alkaline phosphatase and urinary crosslaps were significantly higher in men with FEI, c-bioE(2), and E(2) in the lower quartile than in men with FEI, c-bioE(2), and E(2) levels in the higher quartile. No statistically significant differences were observed in relation to T, c-bioT, or FAI levels. Finally, the ratio between E(2) and T, an indirect measure for aromatase activity, increased significantly with age and was higher in normal than in osteoporotic subjects. In conclusion, results from the present study indicate an important role of estrogens, and particularly of the ability to aromatize T to E(2), in the regulation of bone loss and bone metabolism in elderly men.

Aged↗
PubMed2003

Clinical review 165: Markers of bone remodeling in metastatic bone disease.

Many cancers have a strong propensity to spread to bone. The processes involved in cancer dissemination to bone are complex and variable, and the changes in bone metabolism, once bony metastases have occurred, are usually profound. This review surveys the usefulness of bone markers in the diagnosis and follow-up of patients with malignant bone disease. In patients with established bone metastases, most markers of bone remodeling are abnormal compared with healthy controls or cancer patients without bone lesions. Although bone markers may have a potential as diagnostic tools in cancer patients, the available data do not allow final conclusions regarding the accuracy and validity of any of the presently used markers in the diagnosis of bone metastases. As regards monitoring of anticancer therapy, most markers of bone remodeling respond to active treatments. These indices therefore may have the potential to be used in the monitoring of antitumor therapies. However, most if not all of the available evidence on the use of bone markers in monitoring anticancer therapy is observational, and it remains unclear whether they have any beneficial effects on overall outcome. The same is true for their prognostic value, although evidence suggests that suppressed levels of bone formation or high rates of bone resorption are independent predictors of poor survival.

Biomarkers↗
PubMed1996

Longitudinal changes in bone mineral density and bone turnover in postmenopausal women with primary hyperparathyroidism.

The aims of this study were to determine 1) whether primary hyperparathyroidism (PHPT) is associated with accelerated bone loss in postmenopausal women, 2) whether bone mineral density (BMD) and bone turnover change to a similar extent with surgery and hormone replacement therapy (HRT) in these patients, and 3) whether biochemical markers of bone turnover measured at baseline can be used to predict the change in BMD in these patients after different therapies. We studied 33 postmenopausal women with PHPT; their ages at the time of study ranged from 48-80 yr (mean +/- SD, 63 +/- 10). Total body (TB), lumbar spine (LS), and femoral neck (FN) BMD and biochemical markers of bone turnover were measured at baseline and 10-30 months (19 +/- 5) after parathyroid surgery, HRT, or no treatment. BMD was measured in 33 age-matched healthy controls at baseline and at a mean of 24 months. Baseline biochemical markers of bone turnover were measured in controls. In PHPT at baseline, the mean z-score of BMD was -1.25 at TB (95% confidence interval, -1.64 to -0.86), -0.95 at LS (-1.37 to -0.53), and -1.30 at FN (-1.65 to -0.95), whereas the mean z score was 0.45 for serum carboxy-terminal propeptide of human type I procollagen (0.02-0.89), 1.05 for bone alkaline phosphatase (0.38-1.71), 2.38 for 24-h urinary excretion of cross-linked N-terminal telopeptide of type I collagen (NTx; 1.63-3.13), and 2.36 for 24-h urinary excretion of galactosyl hydroxylysine (1.97-2.74). After surgery and HRT, BMD increased and bone turnover decreased during the follow-up. In the untreated group, BMD decreased at TB and FN, and levels of bone alkaline phosphatase, NTx/creatinine, and galactosyl hydroxylysine/creatinine increased. When the rate of change in BMD (percentage per yr) was compared with that in the control group, bone gain was significant at all three skeletal sites after surgery and HRT, and bone loss was significant at TB and FN, but not at LS, in the untreated group. There was a weak, but significant, correlation between baseline urinary NTx and the change in femoral neck BMD in the untreated group (r = -0.36; P = 0.05). We conclude that untreated postmenopausal women with PHPT have low BMD resulting from accelerated bone loss at the TB and FN. Surgery and HRT both restore BMD and bone turnover toward normal in postmenopausal women with PHPT. A single measurement of bone turnover is insufficient to predict BMD changes in individual patients with PHPT.

Aged↗
PubMed2005

Genetic variation in bone growth patterns defines adult mouse bone fragility.

UNLABELLED: Femoral morphology and composition were determined for three inbred mouse strains between ages E18.5 and 1 year. Genotype-specific variation in postnatal, pubertal, and postpubertal growth patterns and mineral accrual explained differences in adult bone trait combinations and thus bone fragility. INTRODUCTION: Fracture risk is strongly regulated by genetic factors. However, this regulation is generally considered complex and polygenic. Therefore, the development of effective genetic-based diagnostic and treatment tools hinges on understanding how multiple genes and multiple cell types interact to create mechanically functional structures. The goal of this study was to connect variability in whole bone mechanical function, including measures of fragility, to variability in the biological processes underlying skeletal development. We accomplished this by testing for variation in bone morphology and composition among three inbred mouse strains from E18.5 to 1 year of age. MATERIALS AND METHODS: Mid-diaphyseal cross-sectional areas, diameters, moments of inertia, and ash content were determined for three strains of mice with widely differing adult whole bone femoral mechanical properties (A/J, C57BL/6J, and C3H/HeJ) at E18.5 and postnatal days 1, 7, 14, 28, 56, 112, 182, and 365 (n = 5-15 mice/strain/age). RESULTS: Significant differences in the magnitude and rate of change in morphological and compositional bone traits were observed among the three strains at each phase of growth, including prenatal, postnatal, pubertal, and adult ages. These genotype-specific variations in growth patterns mathematically determined how variation in adult bone trait combinations and mechanical properties arose. Furthermore, six bone traits were identified that characterize phenotypic variability in femoral growth. These include (1) bone size and shape at postnatal day 1, (2) periosteal and (3) endosteal expansion during early growth, (4) periosteal expansion and (5) endosteal contraction in later growth, and (6) ash content. These results show that genetic variability in adult bone traits arises from variation in biological processes at each phase of growth. CONCLUSIONS: Inbred mice achieve different combinations of adult bone traits through genotype-specific regulation of bone surface activity, growth patterns, and whole bone mineral accrual throughout femoral development. This study provides a systematic approach, which can be applied to the human skeleton, to uncover genetic control mechanisms influencing bone fragility.

Age Factors↗
PubMed1998

Differential effects of systemic prostaglandin E2 on bone mass in rat long bones and calvariae.

Prostaglandin E2 (PGE2) has been shown to possess anabolic properties when administered systemically. All the experiments performed so far examined long bones from animals of varying age and bone status. In this study we compared the changes in bone mass of long bones (femur, tibia and humerus) to those in calvariae after a 3-week daily administration of 6 mg/kg PGE2 into 3-week-old rats. This regimen inhibited body weight gain (by 14.1%) as well as longitudinal growth of long bones (by 2.2-3.5%) but increased their mass. Ash weight (measuring both cancellous and compact bone) increased by 10.1-14.1% but tibial cancellous bone area was elevated by 54%. Radial growth was slightly reduced due to transient inhibition of mineral apposition rate at the periosteal envelope but the expansion of the marrow cavity was inhibited to a greater extent, resulting in an 8.1% increase in the relative compact bone area. The increased bone mass was associated with greater mechanical strength of the femoral neck (24.2% increase in fracture load and 19% in stiffness). In contrast, PGE2 administration did not affect calvarial thickness or mineral apposition rate but increased its density, i.e. reduced the area of marrow spaces due to stimulation of endocortical bone formation at this site. The pattern of bone mass changes documented in this study closely correlates with that of the induced expression of early-response genes following a single dose of PGE2 as we recently reported. These data, therefore, support the hypothesis that in vivo administration of an anabolic dose of PGE2 increases bone formation and augments bone mass largely by stimulating the recruitment of new osteoblasts via induction of the proliferation and/or differentiation of bone marrow osteogenic precursors.

Animals↗
PubMed1983

Effect of aging and castration on the changes in the levels of bone gamma-carboxyglutamic acid-containing protein in bone and serum of female rat.

Using female rats from 2 to 64 weeks old, the changes in bone gamma-carboxyglutamic acid-containing protein (BGP) levels in bone and serum were studied in relation to the changes in calcium metabolism during aging. Intestinal calcium transport, serum phosphorus level, bone origin serum alkaline phosphatase activity and serum BGP content were high in rapidly growing animals and then decreased with aging. Serum BGP content correlated well to bone origin serum alkaline phosphatase activity. Bone density, bone ash content and bone BGP content increased during aging. Bone BGP content was correlated to bone density which indicates the level of bone calcification. Moreover, the effect of castration on calcium metabolism and bone and serum BGP contents were observed in young (10 weeks old) and aged (40 weeks old) female rat at 12 and 24 weeks after operation. Intestinal calcium transport in ovariectomized rat was significantly lower than in sham operated rat. Serum phosphorus level and serum BGP content were increased in castrated female rat. However, serum calcium level and bone origin serum alkaline phosphatase activity did not show a significant change in castrated female rat. Bone density was significantly decreased in aged rat at 24 weeks after operation. During aging or castration, serum BGP content changed more than bone BGP content. The determination of change in serum BGP levels in various disorders of calcium metabolism would be very informative in future study.

1-Carboxyglutamic Acid↗