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[Temporary plugging of cystic bone tumors by bone cement (author's transl)].

Methylmethacrylate bone cement was used to refill bony defects following excisional biopsy of supposed benign or semimalign bone tumors. This procedure offers several advantages: the anatomical situation at the site of the lesion will not be altered, that means the functions of the joint and the continuity and stability of the bone will be preserved; the histological examination of the tissue is possible without a hurry; the follow up of the lesion is easily possible by X-ray-examination; further therapeutic procedures can follow without restriction, for example if the histology discovered an unsuspected malignant tumor or if the follow-up revealed a recurrency. In addition a favorable effect is the necrosis of tumor cells, eventually left behind in the bone, by the action of zytotoxic monomer and heat, originated during the polymerisation of the methylmethacrylate. In benign or semimalignant bone tumors the cement has to be removed after an adequate observation period; at this occasion the cavity again is curetted and then filled with autologous bone grafts. Since 1972 we treated 13 bone lesions by this method of "temporary bone cement plugging". The lesions were 5 giant cell tumors, 2 aneurysmal bone cysts, 2 simple bone cysts, 1 osteosarcoma, 1 malignant lymphoma, and 2 metastases of hypernephroid carcinoma. In the case of osteosarcoma an amputation was performed just after the diagnosis was made. In the other cases no local recurrances up to now were seen.

Adult↗

[Loss of trabecular bone strength and bone quality after 5 years of fluoride therapy for osteoporosis].

In order to evaluate the effect of sodium fluoride (NaF) on bone biomechanical competence, iliac crest biopsies were taken before and after one year of treatment in 12 osteoporotic patients, and before and after five years of treatment in 14 patients. Bone fluoride content had increased significantly after both one and five years of treatment, indicating that the administered fluoride had been ingested. After one year of treatment, no difference was observed in iliac crest trabecular bone ash content. A general trend for decreased bone strength and bone quality was observed, but this was insignificant. After five years of fluoride treatment, an insignificant decrease in iliac crest trabecular bone ash content was observed. A significant reduction of 45% was found in trabecular bone strength (p < 0.05), and an even more pronounced reduction of 58% was found in trabecular bone quality (p < 0.01). The results of this study indicate that long-term administration of sodium fluoride may be detrimental to bone quality, at least as measured in non-loaded iliac crest trabecular bone.

Aged↗

Endogenous nitric oxide causes vasodilation in rat bone marrow, bone, and spleen during accelerated hematopoiesis.

There is a marked increase in blood flow to rat bone marrow during increased erythro- or granulopoiesis. Furthermore, stimulated erythropoiesis increases bone and splenic perfusion, whereas granulopoietic hyperactivity does not. The mechanism behind this hyperemia is unknown. Endogenous nitric oxide (NO) has been shown to be a potent vasodilator in many vascular beds, but its possible role in the regulation of bone marrow, bone, and spleen vascular resistance and perfusion has not been explored. With the radioactive microsphere method, we determined blood flow to bone marrow, bone, and spleen in awake rats. Eight rats were bled heavily (1.5% of body weight), eight others received 10 micrograms/kg recombinant human granulocyte colony-stimulating factor (rhG-CSF) subcutaneously, and eight other untreated rats served as controls. We used 300 micrograms/kg, intraaortal, of the potent NO synthase blocker N-monomethyl-L-arginine (L-NMMA) (Calbiochem, La Jolla, CA). The inhibition of NO formation was subsequently reversed with 1000 mg/kg intraaortal arginine. Marrow vascular resistance was reduced to approximately 30% of control baseline in the experimental rats 10 hours after hematopoietic stimulation with either bleeding or rhG-CSF. Concomitantly, marrow blood flow increased to about 260% of control baseline in the bled rats, while it almost tripled after rhG-CSF injection. Inhibition of NO formation increased marrow vascular resistance in all three groups. After L-NMMA treatment, marrow perfusion was reduced to about 50% of baseline in the bled and 75% in the rhG-CSF-treated rats, while perfusion in the controls remained apparently unaltered. These changes were completely reversed with arginine. The increases in vascular resistance after NO blockade could not be explained by a concomitant change in arterial blood pressure. L-NMMA increased the vascular resistance in the bone and spleen both in controls and in stimulated rats, but since arterial blood pressure rose proportionally, perfusion remained unchanged. We conclude that NO plays an important role in the regulation of both the normal bone marrow vascular tone and the vasodilation that occurs during accelerated hematopoiesis. NO apparently also regulates bone and splenic vascular tone, but less conspicuously than in the stimulated bone marrow.

Animals↗

Bone turnover in cortical and trabecular bone in normal women and in women with osteoporosis.

UNLABELLED: This study is based on the assumption that is bone turnover, shown by the uptake of 99mTc-MDP, indicates a high rate of bone loss in patients with osteoporosis, it could potentially predict bone loss in patients at risk before significant bone loss has occurred. METHODS: Quantitative bone SPECT (QBS) using 99mTc-MDP, expressed as the %ID/cc x 10(-3), was performed in 71 women who had osteoporosis in the lumbar vertebrae, the femoral neck or both, and in 54 age-matched normal female controls. Of the women with osteoporosis, 42 had postmenopausal osteoporosis and 29 had primary hyperparathyroidism (HPT) and osteoporosis. RESULTS: QBS increased with age in the cortical bone and decreased in the trabecular bone of the normal women. Quantitative bone SPECT in the femoral neck was 3.18 +/- 1.20 and was 2.73 +/- 1.06 in the femoral shaft in 20 women with postmenopausal osteoporosis of the femoral neck. In 19 women with HPT and osteoporosis of the femoral neck, the QBS value in the femoral neck was 3.57 +/- 0.92 and in the femoral shaft 3.38 +/- 1.12. These values were also significantly higher for the femoral neck and for the femoral shaft than those of normals. Although QBS values were higher in the lumbar region in 39 women with postmenopausal osteoporosis (4.59 +/- 1.45) and in 27 women with HPT (4.30 +/- 1.52), as compared with the normal group (4.28 +/- 1.61), the difference was not statistically significant. CONCLUSION: This study shows that bone turnover is significantly higher in the cortical bone of women with osteoporosis than in normal women.

Bone Density↗

A longitudinal study of total and regional bone mineral content and biochemical markers of bone resorption in patients with idiopathic hypercalciuria on thiazide treatment.

The effect of thiazides on total body bone mineral content and axial (trunk) and peripheral (arms) bone mass was evaluated. First, dual-energy X-ray absorptiometry was used to study bone mass in 24 patients with idiopathic hypercalciuria and in 22 healthy subjects. Next, the patients were randomized into a group of 14 patients treated with chlorthalidone (50 mg/day) and a group of 10 untreated patients who served as controls; in these two groups biochemical and bone mass studies were repeated 1 year later. Compared with healthy controls, patients with idiopathic hypercalciuria had less bone mass in total body (p < 0.02), arms (p < 0.001), and trunk (p < 0.05). After 1 year, the group of patients treated with thiazides manifested an increase of bone mass in total body (p < 0.0045), arms, and trunk (p < 0.0001) and a decrease in 24-hour calciuria, urinary calcium/creatinine ratio, and serum tartrate resistant acid phosphatase concentration; the untreated group of patients lost bone mass in all three sites. Under baseline conditions, the groups of treated and untreated patients exhibited a negative linear regression between total body bone mass and both urinary calcium/creatinine (r2 = 0.234; p < 0.001) and serum tartrate resistant acid phosphatase concentration (r2 = 0.399; p < 0.0001). Our results confirm the favorable effect of thiazides on bone mass and provide evidence of enhanced bone remodeling in idiopathic hypercalciuria.

Absorptiometry, Photon↗

[Measurement of bone density by ultrasound bone densitometer in normal pregnant women].

The bone mineral density in reproductive aged and pregnant women was measured with an ultrasound bone densitometer (Achilles, Luner Co, USA). Both parameters of bone density on Os calsis, sound of speed (SOS) and broad ultrasound attenuation (BUA) were significantly correlated with bone mineral density in lumbar2-4 measured by dual energy X-ray absorptiometry (DXA) (p < 0.01) in reproductive aged women (mean age; 24.5 +/- 2.3, n = 30). The changes in bone density during pregnancy and at delivery were studied. In a cross-sectional study, no significant changes in SOS, BUA and stiffness were observed, but in a longitudinal study (n = 21), all of these parameters decreased as pregnancy advanced. The markers of bone turnover (serum Ca, alkaline phosphatase, procollagen type 1-C peptide, urinary Ca/Cr and deoxypyridinoline/Cr) did not change during pregnancy. Ten pregnant women with low bone density (less than-1.5 SD mean value) were found. There was no significant difference between the markers of bone turnover in pregnant women with low and normal bone density. The clinical usefulness of the screening of bone density of reproductive aged and pregnant women to detect osteopenia is suggested.

Adult↗

Fibrous dysplasia of bone in the McCune-Albright syndrome: abnormalities in bone formation.

In addition to café-au-lait pigmentation patterns and hyperendocrinopathies, fibrous dysplasia of bone is a major finding in the McCune-Albright syndrome. Activating missense mutations of the Gs alpha gene leading to overactivity of adenylyl cyclase have been identified in patients with McCune-Albright syndrome, but the mechanism leading to the specific development of fibrous dysplasia in bone has not been elucidated. By means of specific peptide antisera and reverse transcriptase polymerase chain reaction in situ hybridization, we show that expression of Gs alpha and its mRNA is critically up-regulated during maturation of precursor osteogenic cells to normal osteoblast cells and that this pattern of expression is retained in fibrous dysplasia. A functional characterization of fibrous dysplastic tissues revealed that the fibrotic areas consist, in fact, of an excess of cells with phenotypic features of pre-osteogenic cells, whereas the lesional bone formed de novo within fibrotic areas represents the biosynthetic output of mature but abnormal osteoblasts. These cells are noted for peculiar changes in cell shape and interaction with matrix, which were mimicked in vitro by the effects of excess exogenous cAMP on human osteogenic cells. Osteoblasts involved with the de novo deposition of lesional bone in fibrous dysplasia produce a bone matrix enriched in certain anti-adhesion molecules (versican and osteonectin), and poor in the pro-adhesive molecules osteopontin and bone sialoprotein, which is in contrast to the high levels of these two proteins found in normal de novo bone. Our data indicate the need to reinterpret fibrous dysplasia of bone as a disease of cells in the osteogenic lineage, related to the effects of excess cAMP on bone cell function. They further suggest that a critical, physiological, maturation-related regulation of Gs alpha levels makes cells in the osteogenic lineage a natural target for the effects of mutations in the Gs alpha gene and may provide a clue as to why bone itself is affected in this somatic, mutation-dependent disease.

Adolescent↗

Fibula grafting for treatment of aggressive benign bone tumor and malignant bone tumor of extremities.

OBJECTIVE: To compare the effect of vascularized and nonvascularized fibula grafting performed for the reconstruction of bone defects after the resection of bone tumors. METHODS: Vascularized fibula grafting was performed in 18 patients with malignant or aggressive benign bone tumor of the extremities. Non-vascularized fibula grafting was performed in 15 patients with giant cell tumor of the radius. All the 18 patients were followed up with radiography, single photon emission computed tomography (SPECT), colored Doppler's sonography (CDS) examinations and functional observation for 2 to 14 years. RESULTS: Vascularized fibula grafts with bone defects of 9 to 26 cm showed good blood supply in emission computerized tomography (ECT) and radiography examinations, and bone union was achieved (Table 1). In non-vascularized fibula grafting cases (Table 2), bone union was not achieved. CONCLUSIONS: The advantages of vascularized grafting are the feasibility of one-stage reconstruction of various tissues and the growth of grafted fibula. It is necessary to adopt vascularized fibula grafting to reconstruct large bone defect resulting from the resection of extensive bone tumors, such as giant cell tumor (GCT), fibrous dysplasia of bone and malignant bone tumors.

Adolescent↗

SEM study on microvascular changes following implantation of bone morphogenetic protein combined with hydroxyapatite into experimental bone defects.

BMP-HAP complex was implanted into a bone defect in the femur of Wistar-strain rats, and animals were allowed to heal for one to 8 weeks prior to sacrifice. Similar bone defects without BMP-HAP complex served as controls. Osseous healing and microvascular changes, as revealed by plastic microcorrosion castings, were subsequently examined under a scanning electron microscope. One week after implantation, sproutings and congregate sinusoidal capillary plexuses and primary bone trabeculae (woven bone) were observed around and between the BMP-HAP complexes. Control specimens revealed a fine and immature sinusoidal capillary plexus arising from sproutings and elongations of pre-existing blood vessels, but bone formation was not observed. At two weeks, newly-formed trabeculae were observed around and on the surface of the HAPs, and a network of thick, newly-formed vessels was observed in intervening space. At three weeks, networks of newly-formed vessels were observed on the surface of the HAPs, and surrounding newly-formed trabeculae had become thickened. At four weeks, bone defects were filled, and HAP was completely embedded in new bone. At eight weeks, the HAP was fused with new bone, and the boundary between the HAP and new bone was unclear. In comparison with comparable surgically created control bone defects without implanted BMP-HAP complex, BMP apparently stimulates new vascularization. Further, implanted BMP-HAP apparently stimulates undifferentiated mesenchymal cells to differentiate into angioblasts and osteoblasts, or vice versa (dedifferentiation).

Animals↗

Osteoconductivity and bone-bonding strength of high- and low-viscous bioactive bone cements.

A study was conducted to evaluate the osteoconductivity and bone-bonding ability of two types of bioactive bone cement, both consisting of apatite and wollastonite containing glass-ceramic powder (AW-P), fused silica glass powder (SG-P), submicron fumed silica as an inorganic filler, and bisphenol-a-glycidyl methacrylate (Bis-GMA) based resin as an organic matrix. The cements had two kinds of formulas: one (dough-type cement; designated DTC) composed of 85% (w/w) filler and 15% resin, which was developed for fixation of the acetabular component in total hip arthroplasty and could be handled manually; and one (injection-type cement; designated ITC) composed of 79% (w/w) filler and 21% resin. ITC was developed for fixation of the femoral component and, because it had a lower viscosity than DTC, could be injected. The DTC and ITC both contained 73% AW-P, 25% SG-P, and 2% fumed silica in the weight ratio of the filler component. Two other types of cement, both of which consisted of 83.3% AW-P or SG-P, 1.7% fumed silica, and 15% resin, were used as reference material (designated AWC or SGC) for a detaching test. Following the packing of bone defects in the rat tibiae with either DTC or ITC, histological examination revealed that the DTC and ITC had both directly contacted the bone and were almost completely surrounded by bone by 16 weeks after the surgery and that no marked biodegradation had occurred at 52 weeks postimplantation. Rectangular plates (2 x 10 x 15 mm) of AWC, DTC, ITC, and SGC were implanted into the metaphysis of the tibia of male rabbits and the failure load was measured by a detaching test at 10 and 25 weeks after implantation. The failure loads of AWC, DTC, ITC, and SGC were 3.65, 2.21, 2.44, and 0.04 kgf at 10 weeks and 4.87, 2. 81, 2.82, and 0.13 kgf at 25 weeks, respectively. Observation of the bone-implant interface by scanning electron microscopy and energy dispersive X-ray microanalysis revealed that all the samples except SGC formed direct contact with the bone and that only AWC-implanted tibiae had a layer of a low calcium and phosphorus level at the bone-implant interface. Results showed that DTC and ITC have excellent osteoconductivity and bone-bonding ability under non-weight-bearing conditions.

Animals↗

Bone morphogenetic proteins in bone tumors.

Bone morphogenetic proteins (BMPs), inducers of ectopic bone formation in vivo, are present in a number of osteosarcomas. BMPs are responsible for reactive bone formation, including periosteal reactions by normal osteoblasts, rather than production of tumorous osteoid by tumor cells. Osteosarcomas producing BMPs contain less-differentiated mesenchymal cells, resulting in a poorer prognosis for those patients. BMPs are also expressed in malignant fibrous histiocytomas (MFHs) of bone and dedifferentiated chondrosarcomas exhibiting undifferentiated features. However, BMPs in MFH do not show any osteoinductive activity in vivo, suggesting that those BMPs may be inactive forms and have additional functions unrelated to bone formation. Among benign bone tumors, BMPs are expressed in osteoid osteomas or osteoblastomas and effect reactive bone formation such as a surrounding sclerosis. BMPs and a BMP receptor (BMPRIB) are also detected in the cartilage cap in osteochondroma, suggesting that BMP signaling via BMPRIB might be involved in the pathogenesis of osteochondroma. Clinically, BMPs have utility as diagnostic and prognostic markers for characterizing the stage of differentiation of mesenchymal cells and mesenchymal tumors, and they may be of value in predicting the prognosis of sarcoma patients. This article reviews the accumulated information on BMPs in bone tumors, including the most recent findings, and discusses the biological and clinical significance of BMPs in bone tumors.

Animals↗

Suppressed bone induction by follistatin in spontaneously hypercholesterolemic rat bone.

Bone inducing activity in demineralized bone matrix (DBM) of young spontaneously hypercholesterolemic (SHC) rats has been shown to be lower than that of aged SHC rats. This study examined the involvement of bone follistatin, an activin-binding protein, in bone induction. Immunoreactive follistatin was higher in DBM from 10-week-old SHC rats (DBM-10wk) than in DBM from 6-month-old SHC rats (DBM-6mo). When DBM without follistatin supplement was implanted, the C-propeptide of type II procollagen and calcium contents on day 12 in implants of DBM-6mo were 68% and 40% higher than those of DBM-10wk, respectively. In contrast, follistatin supplement to DBM decreased C-propeptide of type II procollagen and calcium contents in implants of both DBM-10wk and DBM-6mo, and the levels of these parameters were comparable between DBM-10wk and DBM-6mo, indicating reduced formation of cartilage and bone. These findings suggest that 1) follistatin content in bone matrix decreases with advancing age in SHC rats, and 2) the follistatin interferes with endochondral bone formation. We demonstrate that the lower bone induction of DBM from young SHC rats was partly due to the abundance of follistatin in bone matrix.

Aging↗

Effect of Zn deficiency and subsequent Zn repletion on bone mineral composition and markers of bone tissue metabolism in 65Zn-labelled, young-adult rats.

The objective of the present study was to investigate the effect of changing skeletal Zn load (mobilization/restoring) on bone mineral composition and bone tissue metabolism. For this purpose, 36 65Zn-labelled, young-adult female rats were fed with either a purified diet with sufficient Zn (21 microg/g, control) for 26 days, or deficient Zn (1.4 microg/g) for 12 days followed by 14 days repletion with the control diet. The animals were killed at the onset of the study (reference: n=4), at the end of the Zn deficiency episode (control: n=4; Zn deficiency: n=4), subgroups (n=4) of Zn repleted animals at repletion days 2, 4, 7, 10 and 14, and at day 14 the remaining controls also (n=4). Zn deficiency reduced skeletal Zn concentration from 198 to 155 microg/g of bone dry matter. About half of mobilized skeletal Zn was refilled within 2 days of repletion and was completely restored until the end of the study. Concentrations of bone ash, Ca, P and Mg remained constant (means in bone dry matter: 51% bone ash, 191 mg Ca/g, 95 mg P/g, 4.4 mg Mg/g). Blood plasma concentrations of osteocalcin and daily urinary excretions of pyridinoline PYD and dexoxypyridinoline DPD were unaffected by treatment (mean: 57 ng/ml, 222 nmol/day, 137 nmol/day). Also daily urinary excretions of Ca, P and Mg remained fairly constant (means: 0.26 mg/day, 16 mg/day, 1.5 mg/day). 65Zn autoradiography of femur sections revealed a pronounced Zn exchange in the area of the metaphysis and epiphysis. We conclude that transient mobilization and restoration of skeletal Zn occurs mainly in trabecular bone, and does not involve major changes in bone mass, macro mineral content, or bone tissue turnover in young-adult rats.

Amino Acids↗

Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation.

Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.

Animals↗

Fractures are highly correlated with bone density and inversely correlated with bone turnover markers in autosomal dominant osteopetrosis.

Autosomal dominant osteopetrosis (ADO) is a rare osteosclerotic disorder usually caused by missense variants in the CLCN7 gene, which results in impaired osteoclastic bone resorption. Penetrance is incomplete, and disease severity varies widely, even among relatives within the same family. Although ADO can cause visual loss, osteonecrosis, osteomyelitis, and bone marrow failure, the most common complication of ADO is fracture. We are conducting a natural history study to characterize disease progression and determinants of disease severity. We hypothesized that baseline BMD and bone turnover markers would correlate with self-reported fracture history. We report cross-sectional analysis of baseline data from the natural history study in 54 individuals (42 adults, 12 children). In adults, Z-scores for both volumetric (r&#xa0;=&#x2009;0.87, p&#xa0;<&#x2009;.001) and areal BMD (aBMD) of the LS, and Z-scores for FN, and TH aBMD (r&#xa0;=&#x2009;0.77 to 0.78; p&#xa0;<&#x2009;.001) were correlated with lifetime fracture number. Tartrate resistant acid phosphatase, a marker of osteoclast number, correlated positively with fracture (r&#xa0;=&#x2009;0.52, p&#xa0;=&#x2009;.004) consistent with an adaptive response of higher numbers of osteoclasts among more severely affected individuals. However, fracture number correlated inversely with the bone resorption markers serum C-telopeptide (r&#xa0;=&#x2009;-0.60, p&#xa0;<&#x2009;.001) and urine N-telopeptide/creatinine ratio (r&#xa0;=&#x2009;-0.35, p&#xa0;=&#x2009;.047), suggesting that ADO subjects who have the most reduced osteoclast activity have a greater tendency to fracture. Correlation coefficients between fractures, BMD, and bone turnover markers were similar when limited to the 37 adults with disease-causing CLCN7 variants. There were no statistically significant differences between subjects with the most common CLCN7 variant (G215R), the most common variant in our cohort, compared to other CLCN7 variants with respect to fracture, bone density measures, or biochemical markers of bone turnover. These data demonstrate that bone density and biochemical bone turnover markers are indicators of ADO severity as defined by fracture number.

Humans↗

From bone biology to bone analysis.

Bone development is one of the key processes characterizing childhood and adolescence. Understanding this process is not only important for physicians treating pediatric bone disorders, but also for clinicians and researchers dealing with postmenopausal and senile osteoporosis. Bone densitometry has great potential to enhance our understanding of bone development. The usefulness of densitometry in children and adolescents would be increased if the physiological mechanisms and structural features of bone were given more consideration in the design and interpretation of densitometric studies. This review gives an overview on the most relevant techniques of quantitative noninvasive bone analysis. Furthermore it describes the relationship between bone biology, selected surrogates describing the biological processes and the possibilities of measuring these surrogates specifically and precisely by the different devices. The overall recommendation for researchers in this field is to describe firstly the biological process to be analyzed (bone growth in length, remodeling or modeling, or all together), secondly the bone parameter which describes this process, and thirdly the reason for selecting a special device.

Absorptiometry, Photon↗

Changes in the serum growth factors and osteoprotegerin after bone marrow transplantation: impact on bone and mineral metabolism.

The loss of bone mass often occurs after bone marrow transplantation (BMT), particularly during the early posttransplant period. There are few reports on the role of growth factors and osteoprotegerin (OPG) in the post-BMT bone loss. This study prospectively investigated 110 patients undergoing BMT and analyzed 36 patients who had dual-energy x-ray absorptiometry performed before BMT and 1 yr after BMT. The biochemical markers of bone formation and resorption were measured at the short-term intervals during the year-long follow-up. The serum IGF-I, IGF binding protein (IGFBP)-3, fibroblast growth factor-2, macrophage-colony stimulating factor (M-CSF), and OPG levels were measured before and 1 wk, 3 wk, and 3 months after BMT. The mean bone loss in the lumbar spine and the total proximal femur, which was calculated as the percent change from the baseline to the level at 1 yr, was 5.2% (P < 0.05) and 11.6% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas bone resorption increased, which was indicated by the biochemical markers of bone turnover. The serum IGF-I levels also decreased progressively until 3 wk and then increased to the basal values at 3 months. The serum IGFBP-3 levels decreased progressively until 3 months. The serum fibroblast growth factor-2 levels decreased to the nadir at 1 wk and gradually recovered to the basal values at 3 months. The serum M-CSF levels increased immediately after BMT, which declined to its baseline level by 3 months. The serum OPG levels increased progressively, reached a peak at 3 weeks, and declined thereafter. There were significant correlations between the IGF-I and osteocalcin levels before BMT and at 3 wk after BMT (r = 0.45, P < 0.01; r = 0.54, P < 0.01). During the observation period, the serum IGFBP-3 and M-CSF levels showed positive correlations with the osteocalcin and serum collagen I carboxyl-terminal telopeptide levels, respectively. Although statistically not significant, the OPG levels tended to be positively associated with the serum collagen I carboxyl-terminal telopeptide levels. Significant correlations were observed between the percent changes from the baseline to 1 yr in the bone mineral density at the proximal femur and the serum IGF-I levels at 3 wk and 3 months after BMT (r = 0.52, P < 0.01; r = 0.41, P < 0.05).

Adult↗

Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk.

CONTEXT: Fractures are a major health burden in elderly institutionalized persons. Type 2 diabetes mellitus (DM) has a high prevalence in nursing home patients and has been associated with positive effects on bone mass in younger, community-dwelling elderly. OBJECTIVE: The objective of this study was to investigate whether type 2 DM affects bone mass, bone turnover, or prospective fracture rates in frail, elderly women living in nursing homes. DESIGN, SETTING, AND PARTICIPANTS: This study was a prospective cohort of 583 patients with type 2 DM and 1081 control (CTR) individuals above age 70 recruited from 95 nursing homes in Austria. Patients were enrolled and followed up by mobile study teams. MAIN OUTCOME MEASURES: We performed quantitative bone ultrasound measurements at the calcaneus, radius, and proximal third phalanx, measurements of quadriceps strength, and biochemical parameters of mineral metabolism and bone turnover. Patients were prospectively followed for hip and other nonvertebral fractures over 2 yr. RESULTS: Patients with type 2 DM had significantly higher age-, weight-, and mobility score-adjusted calcaneal stiffness (P < 0.0001), radial speed of sound (P < 0.005), and phalangeal speed of sound (P < 0.05) measurements when compared with CTRs. Mean serum PTH (-20.7%) and osteocalcin levels (-22.3%) were significantly lower (both P < 0.0001) in patients with treated type 2 DM despite comparable low serum 25-hydroxyvitamin D levels and slightly higher adjusted total serum calcium levels compared with CTRs. Important independent determinants of bone turnover in both patient groups were PTH, creatinine clearance, alanine aminotransferase, as well as glycosylated hemoglobin levels, together accounting for 30-40% of its variance. A total of 110 hip fractures occurred during the observation period, corresponding to a hip fracture rate of 3.1% (in CTRs) and 3.4% (in type 2 DM) per 100 patient years; this was not significantly different for CTRs and diabetics. CONCLUSIONS: Decreased PTH levels and higher levels of glycemia independently contribute to lower bone turnover in elderly nursing home patients with type 2 DM. Despite higher bone mass and lower bone turnover, hip fracture risk is comparable with women without DM.

Aged↗