[Bone demineralization caused either by electrodialysis or by the ethylenediamine tetraacetate (EDTA) method and its importance in bone biology and pathology].
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[A 63-year-old patient with worsening general condition, bone demineralization, hypocalcemia and excess parathyroid hormone: late manifestations of pseudohypohyperparathyroidism].
HISTORY AND CLINICAL FINDINGS: A 63-year-old man was hospitalized because of his worsening general condition and weight loss. Physical examination revealed marked thoracic kyphosis with impaired mobility of his back and restricted walking because of pain in the right hip. He also had other bone pains. INVESTIGATIONS: Serum calcium was reduced (1.60 mmol/l) and there was generalized bone demineralization. Subsequently an increased parathormone (PTH) level was noted (499.0 ng/l) as well as markedly increased activity of enzymes involved in bone metabolism, decreased renal excretion of phosphates (4.76 mmol/24 h) and multiple pathological fractures. TREATMENT AND COURSE: The listed abnormalities indicated the diagnosis of pseudohypoparathyroidism (PHP), type 1 b. After treatment had been started with vitamin D (calcitriol 2 x 0.25 micrograms/d) and calcium (calcium gluconate, 3 x 500 mg/d), the levels of calcium, PTH and enzymes in bone metabolism gradually became normal. A cataract operation had to be performed because of calcification of the lens. CONCLUSION: The level of PTH should be determined in patients with extensive bone demineralization and hypocalcaemia. If PTH is raised, PHP should be included in the differential diagnosis. Normalization of serum calcium by calcium substitution and vitamin D administration will normalize PTH and improve mineralization of the skeleton. In this way the debilitating effects of osteodystrophia cystica generalisata (OCG) (Engel von Recklinghausen syndrome) can be prevented. Also, the consequences of extraosseous calcification, such as extrapyramidal symptoms of calcification of the brain-stem ganglia can be avoided if treated in time.
Bone Demineralization, Pathologic↗
An unexpected outcome during testing of commercially available demineralized bone graft materials: how safe are the nonallograft components?
STUDY DESIGN: Radiographic and histologic analyses of commercially available bone graft materials were performed. OBJECTIVE: To compare the osteoinductive efficacy of commercially available demineralized bone matrix material. SUMMARY OF BACKGROUND DATA: The relative in vivo bone formation and toxicology of the nonallograft components the make up various commercially available demineralized bone matrix products are not known. METHODS: An in vivo bone formation model was used in 30 athymic rats. Six different bone grafting materials were tested in subcutaneous and intermuscular locations. After 4 weeks, radiographic and histologic testing of bone formation was performed. RESULTS: Eight of nine rats implanted with Grafton demineralized bone matrix products died 1 to 4 days after implantation of the bone graft material. None of the remaining 10 animals implanted with the four other grafting materials died. The experiment was modified and completed with a lower dose of bone graft material. Pathologic analysis indicated that the cause of death was hemorrhagic necrosis of the kidneys, most likely caused by a toxic effect on the glomeruli and tubules. A possible causative factor may have been the glycerol in the graft material. CONCLUSIONS: Although the volume of Grafton product per kilogram of body weight used in this study was approximately eight times the maximum volume used in humans, the authors believe that this data must be reported because this product is used substantially in clinical settings. In addition, the osteoinductive performance and relative safety of the nonallograft components in all commercially available demineralized bone grafts are not known.
Animals↗
[Bone mass evolution in patients with precocious and advanced puberty treated with LHRH analogs].
OBJECTIVE: Our aim was to know the long-term effects of treatment with LHRH analogs on the bone mass of patients with precocious or advanced puberty. PATIENTS AND METHODS: Forty-six patients (11 boys and 35 girls) received a-LHRH throughout a 2-year period. The diagnoses were precocious or advance puberty alone or associated to other pathologies. The bone mass was indirectly estimated by measuring the cortical thickness (CT) and the metacarpal diameter (BD) of the 2nd, 3rd, and 4th metacarpals, taking as a reference values the results of the longitudinal Aragonese study of the "Andrea Prader" Center. RESULTS: The CT was 1.3 SD at the beginning and decreased to 0.3 SD (p < 0.002) by the end of therapy and continuing losing to reach 0.1 SD after withdrawal. The BA decreased from 0.8 SD to 0.7 SD (p < 0.0002) and continued decreasing to reach 0.5 SD after withdrawal (p < 0.05). The BD went from -0.64 to -0.62 and to -0.9 SD (p < 0.04) after withdrawal. The longitudinal study of the same 18 cases gave similar results. No significant difference was found between sexes. CONCLUSIONS: In precocious or advance puberty, the bone age and the cortical thickness are increased. After two years of treatment with a-LHRH both decreased significantly and stabilized one year after its suppression. The BD does not change during the treatment, but continues losing value thereafter. This loss of bone mass, not well known in this pediatric situation, is probably related to estrogen deprivation and needs the attention of the physician in order to take possible preventative measures.
Adolescent↗
Blood lead, blood pressure, and hypertension in perimenopausal and postmenopausal women.
CONTEXT: Lead exposures have been shown to be associated with increased blood pressure and risk of hypertension in older men. In perimenopausal women, skeletal lead stores are an important source of endogenous lead exposure due to increased bone demineralization. OBJECTIVE: To examine the relationship of blood lead level with blood pressure and hypertension prevalence in a population-based sample of perimenopausal and postmenopausal women in the United States. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional sample of 2165 women aged 40 to 59 years, who participated in a household interview and physical examination, from the Third National Health and Nutrition Examination Survey conducted from 1988 to 1994. MAIN OUTCOME MEASURES: Associations of blood lead with blood pressure and hypertension, with age, race and ethnicity, cigarette smoking status, body mass index, alcohol use, and kidney function as covariates. RESULTS: A change in blood lead levels from the lowest (quartile 1: range, 0.5-1.6 micro g/dL) to the highest (quartile 4: range, 4.0-31.1 microg/dL) was associated with small statistically significant adjusted changes in systolic and diastolic blood pressures. Women in quartile 4 had increased risks of diastolic (>90 mm Hg) hypertension (adjusted odds ratio [OR], 3.4; 95% confidence interval [CI], 1.3-8.7), as well as moderately increased risks for general hypertension (adjusted OR, 1.4; 95% CI, 0.92-2.0) and systolic (>140 mm Hg) hypertension (adjusted OR, 1.5; 95% CI, 0.72-3.2). This association was strongest in postmenopausal women, in whom adjusted ORs for diastolic hypertension increased with increasing quartile of blood lead level compared with quartile 1 (adjusted OR, 4.6; 95% CI, 1.1-19.2 for quartile 2; adjusted OR, 5.9; 95% CI, 1.5-23.1 for quartile 3; adjusted OR, 8.1; 95% CI, 2.6-24.7 for quartile 4). CONCLUSIONS: At levels well below the current US occupational exposure limit guidelines (40 microg/dL), blood lead level is positively associated with both systolic and diastolic blood pressure and risks of both systolic and diastolic hypertension among women aged 40 to 59 years. The relationship between blood lead level and systolic and diastolic hypertension is most pronounced in postmenopausal women. These results provide support for continued efforts to reduce lead levels in the general population, especially women.
Adult↗
Reduced bone mineral density and unbalanced bone metabolism in patients with inflammatory bowel disease.
Patients with chronic inflammatory bowel diseases (IBD) are at increased risk to develop osteopenia and osteoporosis. New parameters for the assessment of bone formation and especially bone resorption have significantly improved the diagnostic procedures to characterize bone metabolism. Biochemical characterization of bone turnover in IBD patients may provide important information about the pathogenesis of osteoporosis in this patient population. A cross-sectional study was performed. One hundred forty-nine patients (77 men, 52 premenopausal, and 20 postmenopausal women) with IBD (104 with Crohn's disease [CD] and 45 with ulcerative colitis [UC]) underwent clinical, osteodensitometric, and metabolic bone assessment. Bone mineral density was determined by dual energy X-ray absorptiometry. Bone formation (bone alkaline phosphatase), bone resorption (N-terminal telopeptide of type-I collagen, free desoxypyridinoline, total pyridinoline, and desoxypyridinoline), vitamin D, and parathyroid hormone were assessed. Thirty-six percent of patients with CD and 32% with UC showed osteopenia, 15% with CD and 7% with UC showed osteoporosis. Bone resorption was significantly increased in IBD patients compared to normal controls, whereas bone formation did not show a compensatory increase. Bone formation was even more suppressed in the subset of patients currently treated with corticosteroids. Our data confirm the high prevalence of osteopenia and osteoporosis reported in IBD patients. Furthermore, we provide evidence for an increased bone resorption accompanied by low bone formation in IBD patients. This imbalance of bone metabolism is likely to be one of the reasons for increased bone loss in IBD patients.
Absorptiometry, Photon↗
Model of the mechanism of Ca loss by bones under microgravity and earth conditions.
A comparative characterization of crystal structure, morphology, sizes, and orientation in Ca phosphate precipitation from aqueous solutions, the mineral phase in bones, and mineral deposits on cardiac valves has been performed by high-resolution transmission electron microscopy to model possible mechanisms of Ca loss by bones. Physiological changes occurring in organisms can lead to deep perturbations of the natural calcium phosphate supersaturation and its local distribution, which in turn influences the phase composition, morphology, and organization of the mineral phase. Formation of crystals with larger size or of two distinct phases instead of the single hydroxyapatite one can result in the deterioration of the Ca balance in bone and tissue destruction as well as the possible misorientation (or spread of orientation) between HAP crystals newly formed in the bone.
Bone Demineralization, Pathologic↗
Bone metabolism in orthotopic liver transplantation: a prospective study.
Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients with end-stage liver disease who were evaluated for orthotopic liver transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26 patients who underwent OLT. Serum and urinary electrolyte and mineral levels, serum liver function test results, and parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT. At baseline, 40.7% of patients had BMD below the fracture threshold (0.800 g/cm2). Using multiple stepwise regression analysis, we found that BMD was significantly (P < .0001) affected by age, serum creatinine level, and PTH level but not by indices of cholestasis or liver function. In the patients who underwent OLT, a 1.4% reduction (P < .006) was observed in BMD 3 months after OLT. Thereafter, BMD returned to pretransplant values. A significant increase in serum BGP was observed after 6 (P < .02) and 12 (P < . 005) months. PTH levels increased progressively 3 (P < .02), 6 (P < . 001), and 12 (P < .0001) months after OLT. This increase did not seem to be caused by cyclosporine-induced nephropathy. It was concluded that osteopenia is a major complication in hepatic cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12 months after OLT indicates metabolic activation of osteoblasts. The increase in PTH levels after OLT warrants further investigation.
Absorptiometry, Photon↗
Spinal bone mineral loss in estrogen-replete, calcium-replete premenopausal women.
After peak bone mass in women is attained, the benefits of increased dietary calcium or supplemental calcium are uncertain. In a longitudinal, 4-year study we have investigated the effect of calcium intake on bone mineral in a group of 41 premenopausal women, aged 38-42 years at entry. Skeletal density was measured four times during the 4-year follow-up; spinal trabecular bone density (STBD) was measured by quantitative computed tomography, and midradius bone mineral density (RBMD) was measured by single photon absorptiometry. At baseline, no differences in bone density were observed among subjects in the highest and lowest quartiles of habitual dietary intake. Overall, STBD declined -0.86 +/- 0.15% per year (p < 0.001), but RBMD did not decline. Total calcium intake (dietary calcium plus supplemental calcium) did not correlate with the rate of STBD loss. Serum estradiol level did not decrease during the study, and bone loss did not correlate with the mean estradiol level. We conclude that premenopausal women in the fifth decade lose about 1% of spinal trabecular mineral yearly, in spite of a normal serum estradiol level and ample calcium intake.
Adult↗
Histomorphological confirmation of bone loss in the femoral-metaphyseal tissues of rats with skeletal unloading.
The alteration of mineral content in the femoral metaphysis of rats with skeletal unloading was investigated using a model of hindlimb suspension. Animals were fed for 4 days during the unloading. The femoral length, femoral dry weight and femoral mineral density were significantly decreased by the unloading. The calcium, phosphorus and zinc contents in the femoral metaphysis were appreciably reduced by the unloading, although, except for zinc, similar decreases were not seen in the femoral diaphysis. Moreover, the trabecular bone at the femoral metaphysis was clearly reduced by the unloading. Skeletal unloading caused a decrease in osteoid tissue in the primary and secondary spongiosa, indicating that osteoblastic bone formation may be inhibited. The present results clearly demonstrate that skeletal unloading can induce bone loss in the femoral metaphysis.
Animals↗
Kinetics of elemental content changes of bone tissue of mice during evolution under hypokinetic stress.
Concentration of 13 elements in bone tissue of mice held in tightly spaced cages for 3 wk, which caused an acute stress reaction, was determined by means of neutron activation analysis. Functionally different bone tissues of mice skeletons--the femur, accomplishing both supporting and dynamic functions; the parietal bone, being practically immovable; and the ectopic bone, newly formed under kidney capsule in the place of syngeneic bone marrow implantation--were analyzed. Similar dynamics of the elemental composition of investigated bones was found: the progressive demineralization owing to the loss of Ca, P, Mg, and Fe is accompanied by the compensatory inclusion of Sr in the bone tissues. In the ectopic bone, it was not as high. During evolution under hypokinetic stress, the microelement concentrations (Zn, Cr, Rb, Ru, Br, Co, Sb) change significantly. Results obtained form the evidence for some system character of osteoporosis at limited mobility.
Animals↗
[Bone regeneration stimulated by bone substitute materials].
Prompted by severe problems in autogeneic and allogeneic bone transplantation, intensive efforts were made to find sufficient substitutes. A main demand on these materials, especially in healing of osseous defects, is to achieve results comparable to those of auto- or allografts. These must be related to their biomechanical and particularly to their biological properties, i.e. the ability to form new bone, osseous integration and physiological remodeling. Within different trials in the tibiae of sheep we investigated bone substitutes like hydroxyapatite ceramics (HA) or partially demineralized bone matrix (pDBM) and compared them to the gold standards of autogeneic and allogeneic bone transplantation. Therefore we used two different models: the drill hole model with small size defects of 6 mm in diameter and the shaft defect model as a true-to-life defect with a 5 cm large diaphyseal defect. Evaluation was done by X-rays, histology, microradiography, fluorescent microscopy and morphometry of the small size defects. HA showed only small effects on new bone formation and works merely as an osteoconductor. However, excellent new bone formation was regularly achieved by pDBM in the small defects, whereas it was limited in the large size defects. But considering their mechanism of action, it is possible to bridge large bone defects by pDBM.
Bone Demineralization, Pathologic↗
Continuous loss of bone during chronic immobilization: a monozygotic twin study.
Acute immobilization is associated with rapid loss of bone. Prevailing opinion, based on population cross-sectional data, assumes that bone mass stabilizes thereafter. In order to address whole-body and regional skeletal mass in long-term immobilization, monozygotic twins were studied, one of each twin pair having chronic spinal cord injury (SCI) of a duration ranging from 3 to 26 years. The research design consisted of the co-twin control method using 8 pairs of identical male twins (mean +/- SD age, 40 +/- 10 years; range 25-58 years), one of each set with SCI. The twins were compared by paired t-tests for total and regional bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry. Linear regression analyses were performed to determine the associations of age or duration of injury with the differences between twin pairs for total and regional skeletal bone values. In the SCI twins, total-body BMC was significantly reduced (22% +/- 9%, p<0.001), with the predominant sites of reduction for BMC and BMD being the legs (42% +/- 14% 35% +/- 10%, p<0.0001), and pelvis (50% +/- 10% and 29% +/- 9%, p<0.0001). Duration of SCI, not age, was found to be linearly related to the degree of leg bone loss in SCI twins (BMC: r(2) = 0.60, p<0.05; BMD: r(2) = 0.70, p<0.01). Our findings suggest that pelvic and leg bone mass continues to decline throughout the chronic phase of immobilization in the individual with SCI, and this bone loss appears to be independent of age.
Absorptiometry, Photon↗
Protracted systemic changes in bone biology after segmented unloading in the rat.
To investigate whether the decreased bone formation observed in most experimental situations of disuse was caused by an increased inhibition by the bone microenvironment of osteoblast (OB) proliferation, we studied the inhibiting power on ROS 17/2.8 proliferation of the bone marrow extracellular fluid (IPEF) in loaded and unloaded bones of rats submitted to two situations of partial disuse: tail suspension (TS) for 3 days to 2 weeks and around the knee tenectomy (KT) for 2-10 weeks. Histomorphometric parameters and osteoblast precursors dynamics were studied in parallel. Bone volume was lost in the unloaded bones, but not in loaded bones, in both experimental situations. Bone formation was low at early times (7-14 days) in TS rats. However, in KT at later times (4-10 weeks), the osteoblastic index of the unloaded tibia was increased. IPEF was not increased in the unloaded bones 3-7 days after TS. It was decreased later in the course of unloading (after 2 weeks of TS and 2-10 weeks after KT). This decrease was observed in the loaded bones as well. Unexpectedly, we also found that the number of FCFUs was decreased in both loaded and unloaded limbs in TS and KT, and that the yield of cells obtained in primary culture from tibial metaphysis was decreased in both tibiae from KT animals. These data show that an increased IPEF does not play a role in the early inhibition of bone formation responsible for the loss of bone after unloading in the TS model. Its later decrease could be permissive for the increased osteoblastic index observed in the KT model. They also show that, contrary to the usual assumptions, bone biology is changed all over the skeleton after partial unloading, even if the changes result in bone loss in the unloaded bones only. Thus, as yet, unidentified systemic factors probably superimpose on the local factors that control bone volume.
Animals↗
Bone density, vitamin D status, and disordered bone remodeling in end-stage chronic liver disease.
Hepatic osteodystrophy occurs in up to 50% of patients with chronic liver disease (CLD). The aim of this study was to determine the relative contribution of increased resorption and decreased formation to hepatic osteodystrophy by measuring biochemical markers. Twenty-seven patients with advanced CLD (14 female, 13 male) were enrolled. Bone mineral density (BMD), measured at the lumbar spine, and femoral neck, were measured by dual energy X-ray absorptiometry (DXA); bone turnover was assessed using biochemical markers of bone formation and resorption. Based on WHO criteria, osteoporosis and osteopenia were present in 41% and 18% of patients, respectively. All three markers of bone resorption (free deoxypyridinoline, pyridinoline, and hydroxyproline) were increased significantly in patients with CLD. There was a less marked change in the markers of bone formation (osteocalcin, procollagen type 1 peptide, and bone alkaline phosphatase), resulting in a negative uncoupling index in 23/27 (85%) of the patients. Only two (7%) patients had biochemical changes consistent with osteomalacia. The results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and therapeutic strategies should be designed to suppress bone resorption, especially in preparation for liver transplantation. Bone biomarkers may be useful alternatives to bone biopsy in evaluating hepatic osteodystrophy.
Absorptiometry, Photon↗
Bone mineral density of the proximal femur after unilateral cementless total hip replacement.
It was the aim of this study to examine bone mineral density changes in the non-operated contralateral femur of patients undergoing total hip replacement. Bone density in the contralateral femur of 45 patients with an average age of 54 years was measured with the aid of the DEXA technique at one week, 3 and 6 months after total hip replacement. Within the first 3 months there was an average reduction of bone density of 3.9% (3.0%-5.9%). After a further 3 months the average difference was 2.5%.
Absorptiometry, Photon↗
Bone loss in the contralateral asymptomatic hand in patients with complex regional pain syndrome type 1.
Regional osteoporosis was seen radiographically in clinically affected areas in patients with complex regional pain syndrome type 1 (CRPS1). The aim of the this study was to investigate whether bone loss developed in the contralateral hand in patients with unilateral CRPS1 of the hand. Thirty-two patients with CRPS1 of the hand were included in this study. Bone mineral density was measured in the left proximal femur and both ultradistal radiuses, using dual-energy X-ray absorptiometry. The subjects were classified as grades 1 to 3 according to the T-score of both ultradistal radiuses (densitometric grades): grade 1, both radiuses were normal; grade 2, bone loss was determined only in the affected radius; and grade 3, there was bone loss in both radiuses. Twenty (62.5%) patients had bone loss in the affected hand; 11 patients (34.4%) had bone loss only on the affected side and 9 patients (28.1%) had bone loss on both sides. The mean duration of the period between the diagnosis of the injury and the measurement of bone density was 1.9 +/- 0.6 months in patients with grade 1, 3.1 +/- 1.0 months in patients with grade 2, and 5.5 +/- 2.2 months in patients with grade 3. The Spearman test showed a significant correlation between the period of injury and the densitometric grade ( R = 0.774; P = 0.0001). In conclusion, the current study of patients with CRPS1, showed that the bone loss in the asymptomatic contralateral hand developed at a later stage than that in the affected hand. This bone loss was less frequent and of a lower degree in the asymptomatic contralateral hand than in the affected hand. The bone loss in the asymptomatic contralateral hand could be explained by the loss of sympathetic tone in CRPS1 and contralateral sympathetic innervation.
Absorptiometry, Photon↗
A novel therapeutic vaccine approach, targeting RANKL, prevents bone destruction in bone-related disorders.
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Animals↗