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Biomedical subjects

H W Minne

Publications and source records attributed to H W Minne.

At least 19 recordsLinked to original sources
PubMed1992

Does immobilization influence the systemic acceleratory phenomenon that accompanies local bone repair?

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as the regional acceleratory phenomenon (RAP). We previously showed that restoration of a local bone defect in the rat leads not only to RAP but also leads to a systemic acceleration of osteogenesis (systemic acceleratory phenomenon, SAP) in distant sites of the skeleton. In this study we investigated the impact of immobilization of the defect-bearing extremity on the development of SAP. A hole 1.2 mm in diameter was drilled in the diaphysis of the left tibia of female rats. In the experimental group (n = 15), a knee tenotomy was performed in the defect-bearing left hind leg. We examined both femora, both tibiae, and the fourth lumbar vertebra by computed x-ray densitometry on day 7 postoperatively. Immobilization of the defect-bearing limb led to a decrease in x-ray density not only of the immobilized (p < 0.0001) but also of the contralateral tibia (p < 0.0001). Both femora (p < 0.001) and the fourth lumbar vertebra (p < 0.025) of the experimental group also showed a significant decrease in x-ray density. We previously showed that SAP leads to an increase in x-ray density of both femora. This increase is no longer detectable in animals after immobilization of the defect-bearing limb. Thus we conclude that immobilization interferes with SAP. This suggests the possible dependence of SAP on mechanical load. Furthermore, these data suggest a possible impact of local immobilization on the rest of the skeleton.

Absorptiometry, Photon↗
PubMed1992

Mineral apposition rate in rat cortical bone: physiologic differences in different sites of the same tibia.

The mineral apposition rate (MAR) is a commonly used parameter for the characterization of bone formation and is often determined to test for experimental effects on cortical bone. We investigated whether there are physiologic variations in rat cortical MAR dependent on the side or site of measurement. In our experiment we used female rats. The animals were sacrificed on day 8, after double-fluorochrome labeling with calcein and tetracycline was performed. The MAR was calculated at 3.6, 5.4, 7.2, 9, and 10.8 mm from the epiphyseal growth plate of the lateral as well as of the medial endosteum of both right and left tibiae. We found a physiologic significant difference in the MAR between the lateral and the medial endosteal sites of the same tibia (p < 0.0001), especially near the epiphyseal growth plate. Regarding the same cortical side, there is a significant decrease (p < 0.0001) in the endosteal MAR with increasing distance from the epiphyseal growth plate. We conclude that the observed differences in endocortical MAR must be due to specific mechanical challenges. Because these differences are statistically significant, it is necessary to standardize the area of histomorphometric measurement not only with respect to the distance from the epiphyseal growth plate, but also with respect to the cortical side.

Analysis of Variance↗
PubMed1992

Bone mass of spine and forearm in osteoporosis and in German normals: influences of sex, age and anthropometric parameters.

We measured forearm bone mineral density (BMD) using single photon absorptiometry (SPA) and bone mineral content (BMC) and BMD of lumbar spine by dual photon absorptiometry (DPA). The population consisted of 463 bone healthy subjects, 346 females and 117 males aged 20-85 years. Any underlying bone disease or other diseases known to affect bone mass were excluded by physical examination, thoracic and lumbar radiographs and laboratory screening. Patients with osteoarthritis of lumbar spine were excluded as well as patients taking drugs known to affect bone mass. All bone mass values declined with age. Body height also declined with age by 1.2 cm and 1.8 cm per 10 years (-0.7% and -1%) in females and males respectively. Main effects of age, body height, -surface, -weight and -mass index on bone mass were calculated using multiple regression models. In males and females lumbar BMC measured in gHA depended primarily on body height and secondarily on age. Spinal BMD as measured in g cm-2 was primarily dependent on age and then on height. In females forearm BMD depended primarily on age and then on body surface, in males on body surface only. Using receiver operating characteristic (ROC) analysis the ROC area increased from 0.81-0.85 (n.s.) including body height into spinal BMD values leading to a higher sensitivity of measurements of spinal bone mass in recognizing 58 patients with spinal postmenopausal osteoporosis. Including body surface into forearm BMD measurements ROC area increased from 0.66-0.69 (P = 0.055).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of endogenous and exogenous calcitonin on inflammation-mediated osteopenia in the rat.

Inflammation-mediated osteopenia (IMO) in the rat is characterized by loss of bone mass within 3 weeks after induction of nonspecific inflammation (s.c. talcum injections) in growing rats. Histologically, this shows as marked inhibition of osteoblasts 3 days after the initiation of IMO. The role of calcitonin (CT) was investigated in the present study. A reversible increase of serum CT levels was found after intraperitoneal calcium challenge in rats on day 4 after induction of IMO, which was thought to be a result from calcium efflux from bone. No difference in stimulated serum CT levels between the rats with and without IMO was seen on any other day during 4 weeks after initiation of IMO. Bone loss after IMO was more pronounced in normocalcemic and euthyroid rats with deficiency of endogenous CT (thyroidectomy with parathyroid gland reimplanted) (-12.9%) compared with sham operated controls with IMO (-3.25%). Daily subcutaneous injections of 100 mIU salmon CT in rats with and without IMO did not prevent the development of bone loss. This might have been due to the growing state of rats of this age group. Our results support the hypothesis that endogenous CT physiologically has a bone protective role. They furthermore are consistent with the view that endogenous CT itself is not pathogenetically involved in the development of osteoporosis.

Animals↗
PubMed1991

[PTH-related protein (PTHrP) in serum of patients with tumor hypercalcemia].

Parathyroid hormone-related protein (PTHrP) is a recently described hormone, that was isolated from malignant tumors. It shows many properties of parathyroid hormone (PTH) and is related to the pathogenesis of humoral hypercalcemia of malignancy. Therefore, we analyzed PTHrP in the sera of 30 patients with hypercalcemia of malignancy and compared the values with those obtained in patients with primary hyperparathyroidism, Paget's disease of bone, and normal subjects. PTHrP was quantitated with radioimmunoassay (RIA) using aminoterminal antibodies without and with chromatographical sample purification applying SEP-PAK C18 cartridges. Measurements of PTHrP without sample purification yielded high values in all patient groups. There was no differentiation between patient groups. However, quantitation of PTHrP after SEP-PAK C18 purification of the samples resulted in values above the normal range only in tumour patients. In 30 normal subjects PTHrP levels were 110 +/- 75 pg-eq/ml. Eight out of 30 patients with malignant tumours displayed PTHrP-concentrations above 335 pg-eq/ml. PTHrP levels in patients with primary hyperparathyroidism or Paget's disease of bone were within the normal range. PTHrP concentrations were not affected from renal function. We conclude, that determination of PTHrP after sample purification may contribute to the differential diagnosis of malignant disease.

Aged↗
PubMed1991

Spine deformity index (SDI) versus other objective procedures of vertebral fracture identification in patients with osteoporosis: a comparative study.

Radiologic identification of vertebral fractures is most important in the diagnosis and monitoring of patients with spinal osteoporosis. Different methods, using vertebral height measurements for fracture identification, have therefore been developed. We compared four methods for fracture identification in spinal x-rays of 62 female patients with primary osteoporosis. The methods of Hedlund and Gallagher, Melton et al., and Davies et al. are based on the ratio of heights within one vertebra or of the height ratios of adjacent vertebrae; all three methods result in counting the number of vertebral fractures. The fourth method of Minne et al. relates anterior, middle and posterior heights of the vertebrae between T5 and L5 to the respective heights of T4. The relative vertebral heights of patients with osteoporosis are compared to the respective relative heights (anterior, middle, and posterior) of normal subjects (T5-L5). This allows the identification of fractured vertebrae, as well as a quantification of the extent of deformation due to these fractures (spine deformity index, SDI). The same measurement data of 62 spinal x-rays of anterior, middle, and posterior heights between T4 and L5 were used to detect vertebral fractures by the four different methods. Correlation between the number of identified fractures by the different methods ranged between r = 0.56 and 0.83. On the other hand, we found a remarkable difference in the mean number of identified fractures and a discrepancy in the identification of single vertebrae as fractured or not. All four methods revealed an accumulation of fractures in the midthoracic area and in the region of transition from thoracic to lumbar spine. Vertebral fractures as identified by SDI were not detected by the other three methods in 12-29% of the cases, even if vertebral height reduction was more than 6 mm. The reliability of each method was examined by the determination of "decreasing" number of fractures during follow-up. A decrease in the number of fractures was found in about 25% patients, if using the three methods that count only the number of fractures. We obtained a 3.6% decrease in the number of fractures using the fourth method. Furthermore, the decrease in SDI values in follow-up was within the range of variance. We therefore believe that SDI and related procedures are reliable in quantifying spinal osteoporosis and monitoring during follow-up.

Adult↗
PubMed1991

A systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenomenon (RAP) during healing of a bone defect in the rat.

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as a regional acceleratory phenomenon (RAP). We investigated the local healing process with rats with a burr hole defect (1.2 mm in diameter) in the left tibia. We differentiated an initial phase of bone formation followed by a phase of predominant resorption. To determine whether this regional enhancement of bone formation would result in a systemic impact on bone metabolism, we analyzed both tibiae and femora and the fourth lumbar vertebra. On day 7 both femora of rats with the tibial defect showed a significant increase in computerized x-ray density, dry weight, ash weight, and Ca2+ content. Both tibiae and the fourth lumbar vertebra showed a significant increase in mineralizing surface, mineral apposition rate, and bone formation rate. Because of these results we conclude that a systemic acceleratory phenomenon (SAP) accompanies the RAP. SAP affects only the cancellous, but not the cortical bone compartment. SAP is associated closely with the occurrence of woven bone during the formation phase of the healing process. Thus we assume that woven bone formation plays a pivotal role in the mediation of SAP.

Absorptiometry, Photon↗
PubMed1991

Superior local tolerability of human versus salmon calcitonin preparations in young healthy volunteers.

Possible local and systemic adverse effects following administration of salmon (sCT) and human (hCT) calcitonin (CT) have been evaluated in a double-blind, within-subject, comparative trial in 30 young, healthy volunteers. Each subject received 0.25 and 0.5 mg hCT and 100 IU sCT s.c.. Adverse effects and hypocalcaemia were recorded 1, 3 and 6 h after each injection. Significantly fewer local adverse reactions were observed after hCT (20 or 33%) than after sCT (80%), possibly due to the different vehicles employed (mannitol solution and acetic acid). The most frequent systemic adverse effects were gastrointestinal (nausea, vomiting), which occurred in 80% after 1 h, independently of the CT--preparation used. Hypocalcaemic changes were generally small and lasted longer after sCT. It is concluded that the hCT preparations were better tolerated locally than sCT in young, healthy volunteers, and that there were no differences in the systemic side effects or hypocalcaemic activity.

Adult↗
PubMed1991

Influence of parathyroidectomy, 1,25-dihydroxyvitamin D3 and high dietary calcium intake on demineralized bone matrix powder-induced bone formation in the rat.

Demineralized bone matrix induces ectopic endochondral bone formation. We used this model to study the effect of parathyroidectomy (PTX), 1,25-dihydroxyvitamin D3 treatment, and calcium enriched diet on bone formation in the rat. Hypocalcemia and hyperphosphatemia in PTX rats were corrected by 1,25-dihydroxyvitamin D3 treatment (2 x 12.5 ng/day) or by calcium enriched diet (3% calcium). Serum 1,25-dihydroxyvitamin D3 concentration was decreased in PTX rats and in intact rats with high dietary calcium intake. Calcium content of ectopic new bones (42 days after bone matrix implantation) was reduced in PTX rats compared with intact control rats. This could be prevented by 1,25-dihydroxyvitamin D3 treatment. In contrast, calcium enriched diet led to diminished mineralization of ectopic bones both in intact and PTX rats. We conclude that the effect of parathyroidectomy on bone formation may be mediated by 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 directly stimulates bone formation in this model and this effect is not simply the result of increasing serum calcium concentration.

Animals↗
PubMed1991

Osteolytic activity of Walker carcinosarcoma 256 is due to parathyroid hormone-related protein (PTHrP).

The hypercalcemic Walker carcinosarcoma 256 of the rat is an animal model for humoral hypercalcemia of malignancy. Previous in vivo studies suggested the production of a parathyroid hormone-related protein (PTHrP) by the Walker tumor. Therefore, we have measured immunoreactive PTHrP in serum-free conditioned medium from cells derived from this tumor using an antibody raised against human PTHrP(1-34). Walker tumor cell conditioned medium (WCM) displaced 125I-hPTHrP(1-34) from the antibody in a dose dependent manner, whereas control medium contained no immunoreactive PTHrP. In contrast, we detected no secretion of immunoreactive rat parathyroid hormone (rat PTH) by the Walker tumor cells using a midregional radioimmunoassay for rat PTH. WCM stimulated adenylate cyclase in osteoblast like cells, the dose-response curve paralleling that of hPTHrP(1-34). This effect could be inhibited by the PTH antagonist (8Nle, 18Nle, 34Tyr)bPTH(3-34) and by the addition of anti-hPTHrP(1-34) antibody. Bone resorbing activity of WCM in organ culture (calvaria of fetal rats) was not inhibited by indomethacin and glucocorticoids, suggesting a prostaglandin independent mechanism of osteoclast activation in this model.

Adenylyl Cyclases↗
PubMed1991

Increased incidence of euthyroid and hyperthyroid goiters independently of thyrotropin in patients with acromegaly.

The incidence of palpable goiters, the thyroid functional state and thyroid radioisotope uptake was analyzed retrospectively in 80 patients with acromegaly and 80 patients with prolactinomas. 71% of all patients with acromegaly had an enlargement of the thyroid (goiter); 49% of them had diffuse and 39% nodular goiters. The incidence of goiters in patients with prolactinomas from the same iodine deficient geographic region was only 35% (82% diffuse and 18% nodular). 17.5% of acromegalic patients underwent thyroid surgery before diagnosis of growth hormone excess. 17.5% of acromegalic patients with goiters had autonomous areas in their thyroids and 5% were clearly hyperthyroid. Goiters developed slightly more often in females (74%) than in males (67%). The mean preoperative growth hormone level was higher in acromegalic patients with goiter. The incidence of goiters was positively correlated with the documented time of elevated growth hormone concentration in serum. Two patients with exaggerated response of thyrotropin (TSH) (delta TSH greater than 20 mU/l) to the application of thyrotropin-releasing hormone (TRH) had no goiters. On the other hand most patients (61%) with goiters had a low TSH-response to TRH (delta TSH less than 10 mU/l) representing in part occult autonomy of thyroid function. No patient with prolactinoma has had previous thyroid surgery nor thyroid autonomy. One patient with prolactinoma suffered from Graves' disease and none of the acromegalic patients had this disease. We finally conclude that the elevation of growth hormone leads to increased incidence of euthyroid and hyperthyroid (autonomous) goiters independently of the influence of TSH.

Acromegaly↗
PubMed1991

[Osteoporosis as a cause of pathological fractures].

The risk of bone fractures increases with increasing age. There are two reasons: 1) Accelerated bone loss causes destruction of bone structures and yields reduction in mechanical competence of the skeleton. 2) Increasing risk of falling results from rapid changes in pulse rates or blood pressure but also from reduced consciousness in patients using sleeping pills or sedativa. Inappropriate reactions to stumbling and falling cause increased load on bones during falling. Treatment of osteoporosis must take both aspects into consideration: 1) Drugs such as fluorides, bisphosphonates, calcitonins and oestrogens influence bone metabolism by increasing the bone mass. 2) Gymnastics and training stimulate bone formation; gymnastics and additional physical therapy cause reduction of pain and complaints.

Aged↗