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Biomedical subjects

L Mosekilde

Publications and source records attributed to L Mosekilde.

At least 253 records · Page 14Linked to original sources

Biomechanical competence of iliac crest trabecular bone in autosomal dominant osteopetrosis type I.

Cylindrical horizontal iliac crest trabecular bone biopsies were obtained from 9 patients with autosomal dominant osteopetrosis type I and 18 normal controls of comparable age/sex match. Maximum compressive stress, maximum stiffness, energy absorption capacity and maximum strain were calculated from load-deformation curves after a compression test. Ash density of the bone samples was measured after incineration. The maximum compressive stress was significantly increased in the patient group (12.6 +/- 2.6 (SE) MPa vs. 3.3 +/- 0.4 MPa, p less than 0.01), as was the ash density (0.61 +/- 0.05 g/cm3 versus 0.27 +/- 0.02 g/cm3, p less than 0.01). After correction for ash density (normalized maximum stress) the strength of the trabecular bone samples was still significantly increased in the patients (19.7 +/- 6.4 MPa x cm3/g versus 12.0 +/- 1.2 MPa x cm3/g, p less than 0.01). The maximum stiffness and energy absorption capacity were higher in the patients (p less than 0.01), with a corresponding lower maximum strain value (p less than 0.05). The maximum compressive stress correlated closely to the maximum stiffness and energy absorption capacity in both patients and controls, whereas no correlation to maximum strain was found. The maximum compressive stress thus seems to be representative for the two other biomechanical parameters. No significant correlations between age and maximum compressive stress (R = 0.38), ash density (R = 0.08), or normalized maximum stress (R = 0.45) were observed in type I osteopetrosis, whereas significant age-dependent decreases in maximum compressive stress (R = -0.65, p less than 0.02) and in ash density (R = -0.57, p less than 0.02) were observed in normal individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Sex differences in age-related loss of vertebral trabecular bone mass and structure--biomechanical consequences.

Density, structure, and biomechanical competence of trabecular bone were analyzed on cylinders from the central part of the third lumbar vertebral body (L3) from 91 normal individuals aged 15-91 years (48 males and 43 females). A significant and identical age-related decrease (p less than 0.001) in bone density (apparent ash-density and trabecular bone volume) was found for both males and females. The structural analyses revealed a marked, age-related increase (p less than 0.001) in the distance between the horizontal trabeculae in both sexes. In individuals older than 75 years, this increase was significantly higher for females than for males (p less than 0.05). No other significant sex-related differences could be demonstrated in the age-related changes in the trabecular network. The biomechanical compression tests showed a significant and identical age-related decrease (p less than 0.001) in stress-values in the vertical direction for both males and females. When horizontal cylinders were compressed, a steady decrease of bone strength was seen in males, while in females there was a tendency to a pronounced loss of bone strength around the age of 40-50 years. The present study demonstrated clearly a sex-related difference in the changes in vertebral trabecular architecture with age, with a higher tendency to perforation of the horizontal supporting struts in females than in males. The biomechanical consequences of this in these normal individuals were minor--but might be very marked in osteoporotic patients.

Adolescent↗

The predictive value of quantitative computed tomography for vertebral body compressive strength and ash density.

Whole lumbar vertebral sections (L2 and L3) were obtained from 30 elderly individuals aged 43-95 years, mean 81 years (13 females, 17 males). None of the subjects had had malignant diseases. Quantitative computed tomography (QCT) was performed on an EMI 7070 scanner. One 8 mm slice parallel to the end-plates was obtained from the center of each vertebral body. The trabecular bone mass in each slice was outlined interactively by means of a tracer-ball. A CT-histogram was recorded inside this area, and average CT-values were expressed in Hounsfield Units (HU). The whole vertebral body (L2) was compressed in a materials testing machine. From the central part of L3, vertical cylindrical pure trabecular bone specimens were obtained. The biomechanical competence of these specimens was also assessed by means of a materials testing machine. Finally, all bone specimens were incinerated for determination of apparent ash-density. Highly significant positive correlations were found between average CT-values and (a) stress values of the trabecular bone (r = 0.81, p less than 0.001) and (b) ash-density of the pure trabecular bone (r = 0.81, p less than 0.001). Furthermore, a significant positive correlation was found between CT-values and (a) total vertebral body load (r = 0.72, p less than 0.001), (b) total vertebral body stress (load/cross-sectional area) (r = 0.55, p less than 0.001) and (c) ash-density of the whole vertebral body (r = 0.76, p less than 0.001). It is concluded that quantitative computed tomography gives valid predictions of both vertebral trabecular bone mass and mechanical competence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis.

Thirty-seven patients with postmenopausal crush fracture osteoporosis were randomized to oral cyclic estrogen/gestagen (n = 20) or oral calcium (2000 mg elemental calcium per day) (n = 17). Fourteen in each group completed 1 year of treatment. Iliac crest bone biopsies were obtained after intravital double labeling with tetracycline before and after treatment in 10 patients on estrogen/gestagen and 11 patients on calcium. In the estrogen/gestagen group the activation frequency in trabecular bone decreased from 0.52 + 0.11 (SEM) year-1 to 0.27 + 0.08 year-1 (p less than 0.01). No significant changes were found in resorption or formation periods. The osteoid surfaces and the mineralizing surfaces decreased (p less than 0.05), whereas the decrease in eroded surfaces was insignificant. Furthermore, no significant changes were observed in final resorption depth, wall thickness or bone balance per remodeling cycle. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.002), whereas the lumbar bone mineral content (BMC) increased (p less than 0.01). In the calcium group the extent and thickness of osteoid surfaces decreased (p less than 0.05) without significant changes in activation frequency. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.02). No significant changes were observed in lumbar BMC or the other histomorphometric parameters. The study supports that the positive effect of estrogen/gestagen on BMC can be explained by a reduction in the activation frequency of new remodeling cycles leading to a decreased remodeling space and an increase in mean bone age. There is no evidence of a positive balance per remodeling cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Normal postmenopausal women show iliac crest trabecular thickening on vertical sections.

Trabecular thickness and the trabecular star volume were estimated in 49 normal individuals (20 males and 29 females) using an unbiased sampling procedure consisting of anisotropic, vertical sections, and a corresponding anisotropic test system. Eight-microns-thick undecalcified stained vertical sections were obtained from iliac crest specimens. Implying a trabecular plate model mean trabecular thickness (Tb.Th., microns) was estimated by different methods: (a) the ratio between bone volume and bone surface (Tb.Th.ratio); (b) the mean of the orthogonal intercepts multiplied with pi/4 (Tb.Th.l0); and (c) the mean of random linear intercepts divided by 2 (Tb.Th.l1). Trabecular star volume (Vtr*, mm3), a true three-dimensional size parameter independent on any model, was estimated using linear intercepts in random directions. Significant (2p less than 0.001) correlations were found between the different methods with coefficients of correlation ranging from 0.71 to 0.89. The Tb.Th. ratio was overall higher (155 +/- 31 microns, (X, SD), 2p less than 0.001) than the other linear estimates, Tb.Th.l0: 144 +/- 26 microns and Tb.Th.l1: 135 +/- 27 microns. Estimates based on orthogonal intercepts (l0) were slightly higher (2p less than 0.001) than those from random linear intercepts (l1). Among all the individuals no significant age-related changes were seen in the measured parameters. However, postmenopausal women (greater than 50 years of age) had more thick trabeculae than younger women (2p = 0.03). Intra-individual distribution analysis disclosed that this finding could not be explained by preferential perforation and loss of thinner trabeculae during bone remodeling. Therefore, normal postmenopausal women do increase trabecular thickness with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types.

Cylindrical iliac crest biopsies were obtained from 16 patients with autosomal dominant osteopetrosis after intravital double labeling with tetracycline, and compared with normal age- and sex-matched controls. Ten patients had the radiological type I (5 women, 5 men, aged 17-62 years, mean 42) characterized by diffuse, symmetrical osteosclerosis and enlarged thickness of the cranial vault. Six patients had type II (2 women, 4 men, aged 22-44 years, mean 36), where "Rugger Jersey Spine" and endobone are characteristic findings. Structural studies of cortical and trabecular bone were performed, and trabecular bone resorption and formation rates were studied using dynamic histomorphometry. The total biopsy length (C. Wi) were increased in type I (p less than 0.05), and unchanged in type II. Both types showed increased cortical width (Ct. Wi) (p less than 0.01 and p less than 0.05, respectively), and decreased fractional width of cancellous bone (Cn.Wi/C.Wi) (p less than 0.01 and p less than 0.05). The fractional trabecular bone volume (BV/TV) and trabecular thickness (Tb. Th) were both significantly increased in type I (p less than 0.05), while resorptive and formative indices of trabecular bone remodeling were normal. No difference was found in trabecular bone balance, which was slightly positive in both patients and controls. In type II osteopetrosis the eroded surfaces (OS/BS) were significantly increased (p less than 0.01), as was the total resorptive period RP) (p less than 0.05). The resorption depth (R.D.) was normal, while the resorption rate (MRR) was insignificantly decreased. Many big multinucleated osteoclasts were seen in this type suggesting defective resorptive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Seasonal variation of serum bone GLA protein.

The seasonal variation of serum Bone Gla Protein (BGP) was investigated in 15 normal young individuals (seven women and eight men, aged 27-39 years). Serum BGP exhibited a significant seasonal variation of 23% around the yearly mean (p less than 0.001) with zenith in February and nadir in July. Significant seasonal variations were noted also for serum alkaline phosphatase (p less than 0.01) and serum phosphate (p less than 0.01). Serum calcium, bone mineral content (BMC) and creatinine clearance revealed no significant seasonal variation. The seasonal variation of BGP did not follow the variation in serum total alkaline phosphatase. The seasonal variation of BGP has to be taken into account when using the protein as a marker of bone remodelling activity. The variation was probably caused by changes in the production rate of the protein, since the renal excretion of the protein, as reflected in creatinine clearance, remained unchanged throughout the year.

Adult↗

Cortical bone cross-sectional osteon size in chronic pulmonary insufficiency and regional ischemic states.

Cross sectional osteon diameter (D) and Haversian canal diameter (d) were measured in undecalcified, unstained sections from the mid-diaphysis of femoral bones from 13 patients with long lasting chronic pulmonary insufficiency, 10 patients with unilateral thrombosis of the femoral artery and from sex- and age-matched normal controls. The cross sectional osteon radius (R = the distance travelled by osteoclats), the mean wall thickness (MWT = (D-d)/2 = distance travelled by osteoblasts) and the structural unit balance (B = R/MWT) were calculated. No significant differences were found in R, MWT og B between chronic pulmonary insufficiency patients and normal controls. Furthermore, no significant differences were found between thrombotic or non-thrombotic legs or between thrombotic legs and their normal controls. This part of the study does not support the concept that the distance travelled by the osteoclasts (R) depends on local supply of nutrients and/or removal of waste products. However, in all patients and controls R was larger in the inner zone than in the outer zone (p less than 0.01). This could be explained by the anatomy of the arterial supply to cortical bone supporting the above hypothesis.

Adult↗

Histomorphometric analysis of bone in idiopathic hypercalciuria before and after treatment with thiazide.

Twenty-seven normocalcemic patients aged 11-69 yrs with recurrent renal stone formation and idiopathic hypercalciuria were studied before and after treatment with hydrochlorthiazide (TD) 50 mg twice a day for 6 months. Hypercalciuria was defined as a 24 h renal calcium excretion of more than 7.5 mmol for males and 6.3 mmol for females. Quantitative histomorphometric analysis of iliac crest bone biopsies were performed before and after treatment. TD treatment increased the adjusted serum calcium level (p less than 0.01), whereas no significant effects on the serum levels of phosphorous, alkaline phosphatase or iPTH were found. The urinary calcium/creatinine ratio decreased (p less than 0.01) during TD treatment, whereas no change in the urinary phosphorous/creatinine ratio was found. The histomorphometric analysis revealed a reduction in the extent of eroded surfaces (p less than 0.05) and bone formation rate (p less than 0.05) as well as a decrease in the osteoid thickness (p less than 0.05) during TD treatment. No effect on the trabecular bone volume was found. A reduction in the activation frequency of new remodeling sites and thereby a reduced bone turnover during TD treatment can explain the observed histomorphometric changes. The decrease in osteoid thickness may be related to the increased serum calcium concentration leading to better conditions for mineralization.

Adult↗

A histomorphometric determination of iliac bone remodeling in patients with recurrent renal stone formation and idiopathic hypercalciuria.

33 normocalcemic patients (22 males and 11 females) aged 20-68 years with recurrent renal stone formation and idiopathic hypercalciuria were compared to 33 approximately sex- and age-matched normal controls. Quantitative histomorphometric analysis of iliac crest biopsies were performed after intravital tetracycline double labeling in the patients and in 30 sex- and age-matched normal controls. No difference was found between patients and controls in albumin adjusted serum calcium levels. Serum phosphorus was significantly reduced (p less than 0.01) in the patient group whereas the urinary phosphorus/creatinine ratio was increased (p less than 0.01). The serum calcium phosphate product (S-CaxS-P) was significantly reduced in the patients (p less than 0.05). As expected, the urinary calcium/creatinine ratio was higher in the patient group than in the controls (p less than 0.001). Serum parathyroid hormone was normal. The histomorphometric analysis revealed signs of a moderate mineralization defect (reduced adjusted appositional rate (p less than 0.05), prolonged mineralization lag time (p less than 0.05) and prolonged formation (p less than 0.05)), and an increased extension of eroded surfaces (P less than 0.05) in the patients. The amount of trabecular bone and the balance between the thickness of bone resorbed and later formed per remodeling cycle and all other histomorphometric parameters were found normal in the patients. The combined histomorphometric and biochemical data are best explained by a primary renal phosphate leak leading to hypophosphataemia and a slight mineralization defect. The hypercalciuria may be explained by an enhanced renal production of 1.25-dihydroxyvitamin D secondary to the reduced serum levels of phosphorus. No signs of secondary or primary hyperparathyroidism were observed.

Adult↗

Histomorphometric analysis of bone in metabolic bone disease.

Most of the tools necessary for a detailed study of bone remodeling are now available. These methods will enable us to substitute simple surface-based histomorphometry with pertinent derived variables that reveal more information about the processes going on. Because of the inherent variability of the methods, bone histomorphometry is less well suited for investigations in single individuals. However, in terms of basic investigations of cell and tissue activity in grouped materials of patients with metabolic bone disease and the evaluation of treatment regimens in these materials, bone histomorphometric investigations still yield the most detailed analyses.

Animals↗

[Hormonal regulation of bone remodeling].

In the adult skeleton a continuous turnover of bone matrix and mineral takes place at discrete foci throughout life (bone remodeling). This process ensures the mechanical integrity of the skeleton and plays an important role in calcium homeostasis. It constitutes a very complex sequence of events, involving activation of several different stem cell populations and rigid regulation of two contrasting processes: bone resorption and bone formation. The study of factors involved in the control of bone remodeling is complicated by the involvement of local factors (growth factors, prostaglandins, inorganic ions) and systemic factors (calcitropic hormones), that interact at several different levels (cellular, tissue, and organ-levels). Most metabolic bone diseases, including osteoporosis, are caused by disturbances in the regulation of bone remodeling leading to an imbalance between resorption and formation. To understand these disturbances fully, it is necessary to study the different levels of skeletal organization, and the effect of different hormones and local factors on bone resorption and formation. In this review are described the effects of calcitropic hormones on bone cells at the cellular and tissue levels, and their interaction with local factors.

Bone and Bones↗

Chronic sclerosing osteomyelitis of the iliac bone. Etiological possibilities.

An adolescent with chronic recurrent multifocal osteomyelitis located to both iliac bones and an adult with pustulotic arthro-osteitis, involving the left iliac bone, an invertebral space, and the sternoclavicular, first sternocostal, manubriosternal and single peripheral joints are described. Their iliac bone changes were identical, except for the occurrence of bilateral changes in the adolescent, and ankylosis of the sacroiliac joint in the adult. It is suggested that chronic recurrent multifocal osteomyelitis and pustulotic arthro-osteitis may be related diseases with age-dependent differences.

Adolescent↗

Iliac crest trabecular bone volume as predictor for vertebral compressive strength, ash density and trabecular bone volume in normal individuals.

Whole vertebral bodies (L2) and cylindrical trabecular bone samples from the central part of the first lumbar vertebral body (L1) were obtained from 42 normal individuals aged 15-87 years (27 females and 15 males). These bone samples were analyzed by a compression test, and maximum load and stress values were calculated from the load deformation curves. After the compression the ash density of the samples was estimated. For histomorphometric measurements trabecular bone samples from L1 (n = 42) and from the iliac crest (n = 25) were embedded undecalcified, cut in 8 microns sections and stained with Masson trichrome. Trabecular bone volume (TBV) was measured by means of point counting. A significant and parallel age-related decrease in TBV was found in the iliac crest and in the vertebral trabecular bone specimens (p less than 0.001). Highly significant positive correlations were observed between iliac crest TBV and the quantitative vertebral parameters: TBV and ash density (p less than 0.001). Furthermore, the iliac crest TBV was significantly correlated to the qualitative vertebral strength parameters: Vertebral trabecular bone stress, whole vertebral body stress and whole vertebral body load (p less than 0.001). Multiple regression analyses revealed that the vertebral trabecular bone strength was unrelated to bone volume when the influence of age was considered but significantly inversely correlated to age when bone volume was taken into account. This indicates that age-related structural changes other than bone mass affect the vertebral bone strength strongly.

Adolescent↗

Triiodothyronine stimulates urinary excretion of calcium and hydroxyproline in autosomal dominant osteopetrosis.

Six patients with autosomal dominant osteopetrosis were treated orally with 100 mcg. triiodothyronine (T3) daily for seven days. The effect of T3 on bone remodelling was monitored. T3 treatment increased serum T3 from day 1 to 7 (p less than 0.02) with a corresponding fall in serum T4 (p less than 0.01) and serum TSH (p less than 0.02). The levels of thyroid hormones returned to initial levels within the observation period. The renal excretion of calcium and hydroxyproline increased significantly (p less than 0.05) on day 7 and 14 respectively, while there was no significant increase in phosphate excretion. No significant changes were observed in serum calcium, phosphate, or osteocalcin during the study. The observed changes suggest that bone resorption in autosomal dominant osteopetrosis is stimulated by exogenous administration of T3.

Adult↗