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Background and purpose - The minimally invasive direct anterior (DA) approach for total hip arthroplasty (THA) is supposed to reduce surgical tissue trauma. We hypothesized that patients operated with the DA technique would have less postoperative pain and better hip function compared with a group operated with a conventional direct lateral (DL) approach. Patients and methods - 100 patients with hip osteoarthritis scheduled for THA were equally randomized to surgery through either DA or DL. Pain was assessed on a VAS scale, hip function with TUG, 10mWT, HHS, and quality of life with EQ-5D. Patients were followed up after the first 3 days, 8 weeks, and at 1 and 5 years postoperatively. Results - The DA group registered less pain with activity on the second day (VAS 42 vs. 55), performed TUG 6 seconds faster on the third day and had 8 points higher HHS and higher EQ-5D index (0.86 vs 0.78) at 8 weeks; all differences were statistically significant. No clinically relevant differences between groups in pain, hip function, or quality of life were seen at 1 or 5 years. 7 surgical approach related complications appeared in the DA group, none in the DL. Interpretation - The results indicate that the presumably less traumatic approach results in reduced immediate postoperative pain and better hip function and higher quality of life in the early postoperative period. However, this positive effect is not seen at later time points. Instead, complications appear to be over-represented, thus questioning the use of the method.

Collagen-induced arthritis (CIA) is a widely used model of human rheumatoid arthritis (RA) characterized by chronic inflammation of the synovial joints. The pathogenesis of RA and CIA has not been completely defined, but both involve the recruitment of leukocytes and lymphocytes to the joints and Th1-type cell mediated autoimmune responses. The C-C chemokine receptor 5 (CCR5) is preferentially expressed on Th1 cells and has been strongly implicated in inflammatory process through trafficking of leukocytes and lymphocytes into the sites of inflammation. We investigated the role of the CCR5 in CIA using CCR5 knockout mice (CCR5-/-) in which we analyzed the consequences of CCR5 deficiency for the immune response and inflammation. We found that CCR5-/- mice showed a significant reduction in the incidence of CIA after collagen II (CII)-immunization as compared to wild-type (CCR5+/+) mice. The reduced incidence seen in CCR5-/- mice was associated with these animals having significantly lower IgG levels, especially IgG2a and IgG2b antibodies against CII, as well as an obviously augmented IL-10 production in splenocytes. Overproduction of MIP-1beta in CCR5-deficient mice after CII-immunization may contribute partially to the occurrence of arthritis.

Objective: To study the concentration changes of galanin in the ankles and spinal cord and to detect the distribution of galanin in different tissues in arthritic rats., Methods: Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in Freund's incomplete adjuvant at the base of the tail. The concentrations of galanin were measured by radioimmunoassay (RIA) and the distributions of galanin were detected by immunoelectron microscopy (iEM)., Results: Measurements were taken on Day 28 after injection. RIA results showed that the concentration of galanin was significantly lower in the ankles and spinal cords of rats with adjuvant arthritis compared to controls. Our iEM results showed a heterogeneous distribution of galanin labelling in different cells and tissue compartments. In arthritic rats, we observed decreased galanin labelling in the sciatic nerve and in macrophage-like cells in the synovial membrane and increased labelling in monocyte lineage cells, polymorphonucleated lineage cells in the bone marrow, fibroblasts in the periosteum, osteoclasts and osteocytes, and lower labelling in osteoblasts compared to controls., Conclusion: Galanin is involved in the response to inflammation in adjuvant arthritis and might play a role in the regulation of inflammation and nociception. These findings are in accordance with a biological role of galanin in the development of inflammatory arthritis.

Tumor necrosis factor (TNF) and its receptor (TNFR) have been strongly implicated in the pathogenesis of autoimmune disease. Soluble cytokine receptors may be shed naturally from cell membranes to inhibit cytokine activity. Experimental autoimmune neuritis (EAN) is a CD4 Th1 cell-mediated animal model of Guillain-Barré syndrome (GBS) in humans. In the present study, we investigated the effects of soluble TNFR type I (sTNFR I) in EAN induced in mice by P0 peptide 180-199 and Freund's complete adjuvant. Our data from two different therapeutic regimens indicate that the administration of sTNFR I effectively ameliorated the clinical and pathological signs of EAN, i.e., decreased its severity, shortened its duration, and reduced inflammatory cell infiltration into the peripheral nervous system. The suppression of clinical EAN was accompanied in vitro by a marked reduction in antigen-specific T-cell proliferation and IFN-gamma synthesis by spleen cells from sTNFR I-treated mice, compared to control mice treated with PBS. These data directly demonstrate a pivotal role for TNF in the development of EAN and also suggest that sTNFR I may have therapeutic potential for alleviating GBS in humans.

Interleukin 12 (IL-12) is a proinflammatory cytokine with important immunoregulatory activities and is critical in determining the differentiation and generation of Th1 cells. For the present study, we investigated the role of endogenous IL-12 in the pathogenesis of experimental autoimmune neuritis (EAN), which is a CD4+ T-cell mediated autoimmune inflammatory disease of the peripheral nervous system. EAN is used as an animal model for Guillain-Barré syndrome of humans. Here, EAN was established in IL-12 p40 deficient mutant (IL-12-/-) C57BL/6 mice by immunization with P0 peptide 180-199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. In these IL-12-/- mice the onset of clinical disease was delayed, and the incidence and severity of EAN were significantly reduced compared to that in wild-type mice.The former group's clinical manifestations were associated with less P0-peptide 180-199 induced secretion of interferon-gamma (IFN-gamma) by splenocytes in vitro and low production of anti-P0-peptide 180-199 IgG2b antibodies in serum. Fewer IFN-gamma and TNF-alpha producing cells, but more cells secreting IL-4, were found in sciatic nerve sections from IL-12-/- mice, consistent with impaired Th1 functions and response. However, the IL-12 deficiency appeared not to affect P0 peptide 180-199-specific T-cell proliferation. These results indicate that IL-12 has a major role in the initiation, enhancement and perpetuation of pathogenic events in EAN by promoting a Th1 cell-mediated immune response and suppressing the Th2 response. This information augments consideration of IL-12 as a therapeutic target in Guillain-Barré syndrome and other T-cell-mediated autoimmune diseases.

We investigated the effect of ovariectomy (OVX) and hormonal treatment for 10 weeks by estradiol and progesterone on muscarinic M(4) receptor subtype in different brain areas of female rats. Moreover, motor activity of OVX and hormone-treated rats was measured by automated open field exploration boxes. Receptor quantification in the hippocampus, frontal cortex, parietal cortex, amygdala and hypothalamus was done by receptor autoradiography using a selective ligand for muscarinic M(4) receptors. Ovariectomy up-regulated M(4) receptors in the dentate gyrus, CA1, CA3, frontal cortex and hypothalamus whereas the estrogen treatment restored M(4) binding to that of the sham group. Progesterone treatment had no effect on the ovariectomy-induced up-regulation of M(4) receptors. Ovariectomy significantly decreased the exploratory activity of the rats compared to the sham group. Estrogen treatment restored the exploratory behavior of the ovariectomized rats to that of the sham group whereas the progesterone-treated rats were less alert to the surrounding when compared to the sham and estrogen supplemented rats. The effect of estrogen on the hippocampal muscarinic M(4) receptor subtype is a novel finding and may have functional significance for cholinergic receptors especially in relation to postmenopausal memory problems and neurodegenerative disease like Alzheimer's disease., (Copyright 2002 Elsevier Science B.V.)

The distribution and concentration of leu-enkephalin in periosteum, cortical bone, bone marrow and synovial membrane of normal rats were analysed. Periosteum, cortical bone and bone marrow of the rat femurs were collected as well as the ankles. The distribution of leu-enkephalin was analysed by immunoelectron microscopy and the concentration of leu-enkephalin was measured with radioimmunoassay. Immunoelectron microscopy showed that leu-enkephalin is abundant in monocytes of bone marrow, nerve fibers and endothelial cells in the periosteum and also in macrophage-like-cells of the synovial membrane. The concentration of leu-enkephalin measured by RIA showed highest concentration in bone marrow followed by periosteum and cortical bone. The study supports that leu-enkephalin is present and can be quantified in different compartments of bone and joint tissues suggesting that leu-enkephalin may be involved in the physiological regulation of nociception and immunoregulation., (Copyright 2002 Elsevier Science Ltd.)

Adjuvant-induced arthritis (AIA) is a widely used animal model of human rheumatoid arthritis (RA). We have previously shown that increased neuropeptide expression is observed in the spinal cord of AIA rats. To study the potential role of cytokines in the spinal cord of AIA, we wanted to determine whether there are changes of glial and cytokine expression (IL-1 beta, IL-6, TNF-alpha and IFN-gamma) in the spinal cord of AIA rats. Our data indicated that macroglia and MHC class II immunostaining were enhanced, astrocytes expressing GFAP were increased in number and immunostaining intensity. Using in situ hybridization and immunohistochemical methods, both mRNA and protein levels of IL-1 beta, IL-6 and TNF-alpha were significantly increased in the spinal cord of arthritic rats. Increased cytokine expression was presented in the reactive astrocytes and microglia.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are known to play an important role in bone metabolism. The regulation of plasma levels of GH and IGF-I by ovarian steroids is well known, however, their effect on local GH and IGF-I is still unclear. In this study, we investigated the effect of ovariectomy and ovarian steroid treatment on the femur GH and IGF-I levels as well as on bone density in the rat. Nine month-old rats were ovariectomized (OVX) or sham-operated (SHAM) and 9 weeks after the surgery they were treated with daily s.c. injections of either 17beta-estradiol (OVX + E), progesterone (OVX + P), or vehicle (OVX + V) for another 10 weeks. GH and IGF-I levels in the femur extracts were measured by specific radioimmunoassay (RIA). Ovariectomy decreased GH and had no effect on IGF-I levels. Estradiol treatment increased femur GH and IGF-I levels compared to SHAM rats. Progesterone restored GH and increased IGF-I levels. Ovariectomy decreased, estrogen restored and progesterone partially restored femur bone density. Our results demonstrate that ovariectomy and ovarian steroids modulate the levels of GH and IGF-I in the bone of aged OVX rats. However, these effects appear to be limited to supraphysiological concentrations of estradiol and progesterone.

In this study we investigated changes in the spinal cord insulin-like growth factor-I peptide (IGF-I) and its receptors (IGF-IR) after hind limb immobilization for 5 days, 2, 4, and 8 weeks. Moreover, effects on IGF-I and nicotinic cholinergic receptors (nAChRs) in two types of skeletal muscle were also investigated. IGF-I levels were measured by radioimmunoassay (RIA) whereas IGF-IR and nAChRs were measured by quantitative receptor autoradiography. Spinal cord IGF-I levels decreased significantly after 5 days, 2 and 4 weeks of immobilization, whereas IGF-IR increased significantly after 4 and 8 weeks compared to controls. In skeletal muscles, nAChRs increased significantly after 5 days and 2 weeks in the soleus (SOL) and tibialis anterior (TIB) muscles, respectively, and continued up to 8 weeks in both muscles. IGF-I concentration decrease significantly after 4 and 8 weeks in the SOL and TIB muscles, respectively. Despite the normal levels of IGF-I in both muscles at the early time points (5 days and 2 weeks), low levels of IGF-I were observed concurrently in the spinal cord ipsilateral to the immobilized limb. Our findings suggest that the early decrease in the IGF-I level and the late upregulation in the IGF-IR in the spinal cord might represent a nervous system response to disuse.

Levels of somatostatin were investigated in the ankles and spinal cords of rats suffering from acute and chronic adjuvant arthritis. As measured by radioimmunoassay, somatostatin showed significantly higher concentrations only in chronic arthritic ankles. No significant difference was observed in somatostatin levels between the spinal cords of normal and arthritic groups. Using immunohistochemical labeling and electron microscopy, we observed increased somatostatin labeling in the mature bone matrix, monocytes, and polymorphonuclear cells of bone marrow and macrophage-like synovial cells of chronically arthritic rats. Understanding the mechanism(s) which lead to increased somatostatin in chronic arthritic joints may result in more effective treatment methods.

The effects of somatostatin on the development of adjuvant arthritis induced by Mycobacterium butyricum were studied. Somatostatin was injected into the lateral cerebral ventricle every day for 14 days beginning on the first day of mycobacteria inoculation in the preventive group. In the treatment group, somatostatin was injected from day 17 until day 30 post-mycobacteria inoculation. Arthritis was evaluated by measuring ankle joint circumference and diameter as well as microscopic examination of ankle joint sections. Somatostatin profoundly inhibited the development of adjuvant arthritis and an anti-inflammatory action was observed in the treatment group. These results suggest that somatostatin has a central action that can prevent or attenuate symptoms associated with arthritis.

Immobilization of an extremity causes skeletal muscle atrophy and a dramatic increase in bone resorption. Growth hormone (GH) is known to play an important role in bone remodeling mediated in part by local insulin-like growth factor-I (IGF-I). In this study, we investigated changes in the levels of GH and IGF-I peptide in bone extracts from the femur after hind-limb immobilization for 5 days, 2, 4, and 8 weeks. The levels of somatostatin, which interacts with GH, were also measured in the bone extracts. GH levels increased after 8 weeks of hind-limb immobilization whereas the IGF-I concentrations increased after 2 weeks, but returned to control levels at 4 weeks, and decreased after 8 weeks of immobilization. The somatostatin levels in the bone extracts increased only after 8 weeks of hind-limb immobilization. Our findings suggest that, after hind-limb immobilization, changes in the concentrations of GH, IGF-I, and somatostatin in bone may mediate bone resorption either directly or through interaction with other factors.

One hundred fourteen total hip arthroplasties in 110 patients performed between 1979 and 1983 using the Lord femoral component were analyzed. Nine femoral revisions were performed within 13 years after surgery (two because of infection). Excluding infections there was a 94% 13-year survival according to a Kaplan-Meier analysis. Subsidence was seen in five hips (five patients), but only one needed revision surgery. Seventy-six hips (73 patients) had a radiographic followup of 10 years or more and were analyzed in detail. Changes in cortical thickness, density, and formation of spotwelds continued beyond 5 years after surgery, meaning the remodeling of periprosthetic bone continued beyond that time. Osteolysis on the femoral side was seen in seven hips, always in the proximal part of the femur, apparently as a continuation of the joint space. No remote focal osteolysis was seen. Elderly patients, women, and patients with a pedestal were overrepresented among individuals with many spotwelds. For the clinical outcome the Merle d'Aubigne and Postel score as modified by Charnley was used. Among 69 hips (66 patients) with a mean followup of 153 months 96% (66 hips) had a pain score equal to or greater than 4 and 74% (51 hips) had a score of 5 or 6. The Lord femoral component gave surprisingly good clinical long term results despite the bone remodeling (stress shielding), which in some cases was pronounced. The most obvious disadvantage with this design appears to be the difficulties associated with its removal when indicated.

The purpose of this study was to investigate the anti-inflammatory properties of intracerebroventricular met-enkephalin (met-enk) administration in an animal model of arthritis. Adjuvant arthritis was induced in rats by intradermal inoculation of mycobacterium butyricum and the effects of intraventricular met-enk+thiorphan (enkephalinase inhibitor) were studied. Treatment was initiated either simultaneously with the bacterial inoculation (preventive group) or on post-inoculation day 17 after the appearance of inflammation (treatment group). The degree of inflammation was evaluated by measuring the diameter and the circumference of the ankle joint immediately before the sacrifice (day 31) and by histologic examination of ankle joint sections. The results of this study revealed that combined intraventricular injections of met-enk+thiorphan reduced the arthritic-like inflammation in the preventive group as well as in the treatment group. These findings suggest that centrally applied met-enk+thiorphan may suppress the development adjuvant arthritis as well as the symptoms of manifest arthritis. Thus central met-enk may be involved in both hypothalamic pituitary adrenal axis and immune forms of stress-induced modulation.

Immobilisation causes denervation-like changes in the motor endplates, decreases the content of IGF-I, and increases the number of IGF-I receptors in the spinal cord. In the rat we investigated whether similar changes occur after a fracture of the midshaft of the femur which had been treated by intramedullary fixation with adequate or undersized pins. A more pronounced reduction in muscle wet weight was seen after fixation by undersized pins as well as decreased ash density of the ipsilateral tibia which did not completely return to normal within the 12-week experimental period. The nicotinic cholinergic receptors in the motor endplates of tibialis anterior were increased (p < 0.01) and there was a significant increase (p < 0.02) in IGF-I receptors in the lumbar spinal cord ipsilateral to the fracture after treatment by undersized nails. These changes may be associated with the impaired proprioception, co-ordination and motor activity which are sometimes seen after fractures.

We used 111 rabbits to study the susceptibility to intravenously injected bacteria of conventional stainless steel plates, and titanium plates of either traditional design or of the PC-FIX concept, that is less traumatic to bone. After plating, the animals were given between 1 x 10(8) and 2 x 10(9) colony forming units of Staphylococcus aureus Wood 46 intravenously. Significant differences in infection rates (positive cultures) were found between conventional stainless steel plates (36-67% infected, depending on inoculum size) and titanium PC-FIX plates (6-7% infected). In fact, the infection rate at the PC-FIX plate did not differ from sham operated animals. Since conventionally designed titanium plates had an intermediate infection rate, it appears that design and material both are important for the risk of infection.

We used 30 New Zealand white rabbits to compare the susceptibility to bacterial challenge of two different orthopaedic implants: a standard-design stainless steel plate, or a PC-FIX titanium plate applied on the right tibia were compared with sham operated animals. Directly after surgery Staphylococcus aureus (10(8)-10(9) colony forming units) were inoculated close to the plate. The infection rate in the group of plated animals was 11/20 (stainless steel plates 6/10, PC-FIX titanium plates 5/10) and in sham operated animals only 1/10. Thus, a foreign body increased the risk for infection (p = 0.02). However, the implant type did not appear to be of major importance when the bacteria were inoculated locally. In experimental haematogenous infections, by contrast, implant design and material are considered to be important. This may either indicate different pathogenic mechanisms in locally and haematogenously induced infections, or simply that the large number of microorganisms in local inoculation 'overload' the normal defence systems.

The effects of 4 weeks' hind-limb immobilization on the spinal cord insulin-like growth factor-I (IGF-I) receptors and skeletal muscle IGF-I level was investigated in rats. Quantitative receptor autoradiography using [125I]IGF-I as a ligand was performed to measure IGF-I receptors in cryosections from the lumbar region of the spinal cord. IGF-I receptor levels were significantly higher in all spinal cord laminae on the side ipsilateral to the immobilized limb than in the same spinal level of the controls. Using radioimmunoassay (RIA), IGF-I levels were significantly low in the soleus (SOL), but not the tibialis anterior (TIB) muscles, compared to the controls. The enhancement of the spinal cord IGF-I receptors after hind-limb immobilization may constitute part of the nervous system response to disuse.

In this study we have investigated the levels of prolactin, growth hormone, and insulin-like growth factor-1 in plasma and in tissue extracts of ankle joints of rats with acute or chronic adjuvant arthritis using enzyme immunoassay (EIA) and radioimmunoassay (RIA). We found a stable content of prolactin in plasma of the different groups but a significantly increased concentration of growth hormone was observed in the plasma of the group with chronic arthritis. Moreover, an increased concentration of insulin-like growth factor-1 was noted in the plasma of the acute group. This evidently had returned to normal levels in the chronic group. In contrast, decreased concentrations of prolactin, growth hormone, and insulin-like growth factor-1 were found in tissue extracts of ankle joints of the group with chronic arthritis. The changes in the levels of these hormones in adjuvant arthritis might suggest that they play a role in the pathogenesis of the disease. Understanding the mechanism(s) of hormonal participation in adjuvant arthritis may open new treatment strategies for rheumatoid arthritis and other inflammatory disorders.

The localization of neurokinin A (NK-A) in the normal ankle joint of rats was investigated by an immunoelectron microscopic technique with specific antisera to NK-A. Immunoreactivity was detected in bone matrix, myelinated nerve fiber in the periosteum, and bone marrow and synovial cells. No immunoreactivity was observed in osteoblasts, osteocytes, and osteoclasts. Using radioimmunoassay (RIA), a detectable concentration of NK-A was observed in the bone marrow, periosteum, cortical bone, and ankle of normal rats. In rats with chronic adjuvant arthritis, induced by intradermal injection of mycobacterium butyricum in paraffin oil into the base of the tail, the concentrations of NK-A using RIA in ankles and spinal cords were found to be significantly increased compared with acute or control rats. There were no significant differences between the latter two. Similarly, increased NK-A labeling was observed using immunoelectron microscopy in bone matrix and bone marrow monocyte cells of the chronic arthritic rats. These findings indicate the existence of as well as a biological role of NK-A in bone and joint tissues.

Objective: To study whether met-enkephalin (met-enk) concentration changes in adjuvant arthritic ankles and spinal cords., Methods: Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in paraffin oil, into the base of rat tail. The levels of met-enk were measured using radioimmunoassay and high performance liquid chromatography electrochemical detection in arthritic ankle and spinal cord of arthritic and control rats. Protein concentration was measured according to Lowry method., Results: We observed a significant decrease of concentration of met-enk in ankle joints of chronic arthritic rats. However, increased concentration of met-enk was obtained in the spinal cord of chronic arthritic rats., Conclusion: The significant reduction of met-enk concentration in the arthritic ankle joints indicates a possible role for the endogenous opioid peptide in arthritis.

Using immunoelectron microscopy we have investigated the presence of somatostatin in normal bone and joint tissues. We observed somatostatin labeling in the myelinated nerve fibers of the periosteum, the bone marrow cells and in the mature bone matrix but only slightly in the synovial cells. Quantification of somatostatin in bone tissue by radioimmunoassay showed highest levels in bone marrow followed by periosteum and cortical bone. These findings suggest a role for somatostatin in bone and joint physiology.

Methionine-enkephalin (met-enk), an endogenous opiate, mimics many of the effects of morphine by binding to opiate receptors, thereby eliciting similar cellular and behavioral effects. Using biochemical and immunohistochemical techniques, several peptides have been identified in bone and joint tissues. Here we report, for the first time, the presence as well as concentration of met-enk in bone and joint tissues. Immunohistochemistry using electron and immunofluorescence microscopy showed cellular and neuronal distribution of met-enk in bone and joint tissues. The concentration of met-enk analyzed by high performance liquid chromatography electrochemical detection or radioimmunoassay was high in bone marrow, periosteum, ankle joint tissue, and cortical bone. Analysis by fast atom bombardment mass spectrometry suggested that the recovered fragment was met-enk Administration of met-enk inhibits osteoblast cell growth in culture, which is reversible by naltrexone. In arthritic rats, the concentration of met-enk was significantly decreased in ankle joints compared with controls, suggesting a role for met-enk in the pathophysiology of adjuvant arthritis.

The effect of 4 weeks of hind limb immobilization on nicotinic acetylcholinergic receptors (nAChRs) in the neuromuscular junction of the soleus (SOL) and tibialis anterior (TIB) muscles was studied in rats. Quantitative measurements of the receptors was performed using [3H]alpha-bungarotoxin ([3H]alpha-BTx) receptor autoradiography. Junctional and extrajunctional nAChRs were significantly increased in the SOL and TIB after 4 weeks immobilization. However, a significant decrease in fiber cross-sectional area was observed only in the SOL muscle. Remobilization for 4 weeks reversed the changes in cholinergic receptors and muscle fibers but not in bone. Our findings suggested that lack of nerve impulses are of importance for the events that take place after immobilization leading to muscle atrophy and osteoporosis.

Most reports of excellent long-term results of cemented total hip arthroplasty originate from studies of Charnley prostheses. A radiographic and clinical study was performed on 126 patients who underwent a cemented total hip arthroplasty from 1983 to 1985 with the Harris Design 2 prosthesis (Howmedica, Rutherford, NJ). The femoral component was cobalt-chromium and it had a broad, rounded medial border and a collar. The head diameter was 26 mm. A cemented all-polyethylene socket was used in all cases. At the last follow-up examination, 71% of the patients were completely free of pain and no patient had severe pain or pain at rest. Kaplan-Meier survival analysis estimated the revision rate at 10 years after operation to be 5 +/- 2% (mean +/- SEM) (including planned revisions). The rate of complete acetabular demarcation was 20% at 10 years, and femoral demarcation involving more than 50% of the bone-implant surface or endosteal cavitation was noted in only three cases. These results are as good as the best reported after total hip arthroplasty with the Charnley prosthesis.

We studied 70 patients after uncemented hip replacement with the Lord prosthesis which has a relatively long, completely macrotextured stem. The mean follow up was for 9.5 years. We compared radiographs at one year after operation, at 5 years and at the last follow up. Twenty-five patients (36%) had deep or circumferential pain in the thigh. Of the 44 who were most active at 5 years those with thigh pain had less proximal cortical loss than those without (p < 0.05), most cortical bone formation distally and most often had incomplete radiolucent lines at the mid-stem level, perhaps indicating more elastic displacement of the bone relative to the prosthesis. The presence of radiolucent lines correlated with the increase in cortical width at 5 years (p < 0.01). Cortical remodelling continued after 5 years at all levels except at the tip (p < 0.01). The relative elastic displacement at the interface could cause pain and may contribute to the pattern of bone remodelling in the femur after uncemented hip replacement.

We studied the most complete skeletons found in an excavation from the 14th and 15th century in central Stockholm. One hundred eighty-seven were from men and 156 from women: 241 individuals were estimated to be between 20 and 39 and 102 between 40 and 59 years old at death. We examined the bones radiographically and by dual photon absorptiometry. The bone mineral density (BMD) was similar to the finding in North America and Northern Europe today as was the relationship between men and women. However, there appeared to be a higher diaphyseal bone density in the lower extremities, especially in men. The femur score was higher and the BMD of the femoral and tibial shafts was higher than today. In the upper extremities the diaphyseal bone density was lower. Meema's index, as well as the metacarpal score, was smaller than in individuals in this century and the BMD of the humeral shaft was also lower than seen today. Overall, the metaphyseal bone density was similar to what we now consider normal; i.e., the mean BMD of the femoral neck was 0.96 g/cm2 in men and 0.90 g/cm2 in women and of the distal radius 0.43 and 0.32 g/cm2, respectively. The low diaphyseal density and in the upper extremities may be related to the nutritional status, whereas the greater need for walking and standing in the 14th and 15th century might have led to the high diaphyseal density in the lower extremities. There was no evidence of bone loss after 40 years of age in either sex in our study. The average expected lifespan for an adult individual was less than 50 years and we suggest that the relatively high bone density in the older age group may be due to selection of the most physically fit. The activity pattern, therefore, may be considered the most important determinant for the differences.

New methods of treatment have greatly improved the success of limb salvage in severe lower extremity trauma. We report the use of a microvascular free tissue transfer and distraction osteogenesis in the reconstruction of soft tissue and bone defects complicated by infection. Soft tissue coverage and bony stabilization by external fixation resulted in eradication of the infection. The external fixator also allowed bone transport and regeneration to overcome a bone defect of approximately 6 cm. Bone transportation can be accomplished in a distal to proximal direction if the situation necessitates it. These techniques are extremely versatile and useful in the treatment of bone and soft tissue defect.

Twenty-two middle-aged women with severe osteoporosis were treated for 2 years with either 0.5 mg of synthetic human calcitonin subcutaneously three times per week combined with 0.5 micrograms of calcitriol and 0.5 g of calcium per day orally or calcium only. The treatment with calcitonin plus calcitriol (12 patients) resulted in a significantly increased calcium absorption rate. The mean values for serum phosphate did not change during the treatment period and the mean values did not differ between the treatment groups, but the serum calcium and urinary Ca/Cr ratio increased somewhat in the group given the combined treatment. There was no evidence that the combined treatment improved the bone density in this study. It is possible that calcitriol, instead of increasing the effect of calcitonin by suppression of the parathyroid, might have counteracted its effect by increasing the bone resorption.

Eighty-eight adult male Sprague-Dawley rats were given a diet with either (a) 0.5% Ca and 0.6% P or (b) 0.01% Ca and 0.6% P. Osteopenia was created by adding prednisolone to the diet. The prophylactic effect of oral 1,25(OH)2D3 on the osteopenia was studied. It was found that prednisolone osteopenia in the rat was associated with defective Ca absorption. By giving an oral dose of 1,25(OH)2D3, it was possible to maintain normal Ca absorption during prednisolone treatment and to prevent the bone loss. No significant hypercalcemia or any kidney calcifications were seen. These results are in contrast to earlier findings, in which subcutaneous administration of 1,25(OH)2D3 failed to prevent prednisolone osteopenia because of its tendency to increase bone resorption.

Adult male rats were treated for six weeks by prednisolone and/or 1,25-(OH)2D3 and given a diet containing either 0.5% calcium or 0.01% Ca and 0.6% phosphorus. Both prednisolone administration and a low-Ca diet were associated with a lower bone mass than that observed in control rats given a 0.5% Ca diet. The percentage of osteoid surface was decreased in rats given prednisolone; these rats also had a lower osteoclast number. The results were consistent with a lower bone turnover during prednisolone treatment. Administration of 1,25-(OH)2D3, resulting in a slightly higher mean level of 1,25-(OH)2D3 in serum, had a positive effect on bone mass, which may be related to increased osteoblastic activity; no increase in the osteoclast number occurred.

Guinea pigs sensitized to nickel, cobalt, or chromium were used to study if impaired fixation occurred as a result of allergy against metal implants in bone. Screws made from stainless-steel (ASTM F55, F138-139) or cobalt chromium (ASTM F75-76) were inserted in the right and left proximal tibiae, and the mechanical strength of the fixation to the bone was evaluated after 4 months. In addition, we studied the histology on decalcified sections of the implant bone interface from the distal femur where the same type of screws had been inserted. To see if changes in bone density occurred in the proximal tibia as a result of allergy, the amount of ash was determined. Although the animals maintained their contact sensitivity throughout the experimental period, there were no differences between allergic and control animals for any of the parameters studied. All screws were well fixed in the tibia at the end of the experiment, and histologically we did not find any significant differences between allergic and control animals by qualitative examination. The experiment supports our earlier results from a 6-week experiment and indicates that contact allergy may be unimportant for the fate of orthopedic implants.

In order to study the role played by the thyroid and the parathyroid glands in the development of osteoporosis induced by immobilization, 153 male adult Sprague-Dawley rats allocated in two groups were used. The animals of one group were thyroparathyroidectomized; those of the other group were left intact. Each group was then divided into two subgroups; in one the right hind leg of the animals were immobilized by an elastic adhesive bandage. The animals were observed for varying periods of time up to 16 weeks. Studies of bone mass and 45Ca accretion rate of the right and left femur and tibia were performed in all animals. The results indicate that disuse osteoporosis occurs in rats in the virtual absence of the thyroid and parathyroid glands. The bone loss of the immobilized femur and tibia was less pronounced in thyroparathyroidectomized rats compared to intact rats. The uptake of 45Ca in bone treated by immobilization as compared to the non-immobilized bone was found to be increased to the same proportion in thyroparathyroidectomized and in intact rats. The calcium-accretion rate of non-immobilized bone was lower in thyroparathyroidectomized than in intact rats. The observations indicate that in the rat the parathyroid and thyroid hormones influence the rate of bone turnover and thereby the rate of development of disuse osteoporosis.

Combined experimental and clinical research illustrates not only the multiplicity of questions for research on osteoporosis but also the difficulty of penetrating such a complicated clinical problem as treatment and prevention of osteoporosis. Without thorough knowledge of the pathomechanisms responsible for the development of the condition and a rational working hypothesis, any attempt to develop a new approach seems unlikely to succeed.

Fifty adult female rats were used to study the effect of 1-alpha-hydroxyvitamin D3 (1alpha-OH-D3) on bone after oophorectomy. The experimental period was 6 months. At the end of the experiment the femurs and the tibias were investigated for bone mass and composition. Significant signs of osteopenia occurred as a result of oophorectomy. The treatment with 1alpha-OH-D3 induced only minor changes in blood chemistry but increased bone mass significantly. The findings support the view that 1alpha-OH-D3 may be a valuable tool in the treatment of osteoporosis resulting from ovarian insufficiency.

A closed tibial fracture, which was controlled by an intramedullary stainless steel pin, was created in 16 rabbits. Eight rabbits were treated with 75 ng of 1,25(OH)2D3 daily as subcutaneous (s.c.) injections. After three weeks, the fractured tibia resisted a force of 101.7 +/- 21.0 Newtons in the control group and 57.3 +/- 8.0 Newtons in animals given 1,25(OH)2D3 (m +/- SE, P less than 0.05). In another group of eight rabbits, the left hindleg was immobilized in a plastic splint. Four rabbits were given 75 ng of 1,25(OH)2D3/day s.c. and the effect of immobilization was studied on the calcaneus. Bone ash/cm3 of the calcaneus on the immobilized side was decreased by 11 +/- 2% in control rabbits and by 20 +/- 2% in the group treated with 1,25(OH)2D3 indicating a more advanced immobilization osteoporosis (m +/- SE, P less than 0.05), which was also demonstrated by studies of bone density. Eighteen rabbits were used in a study of the effects of 1,25(OH)2D3 on the development of prednisolone osteoporosis. The dose of prednisolone was 2.5 mg per day, given by the oral route. After four months, the density of the femur was 1.53 +/- 0.02 g/cm2 in control rabbits and 1.42 +/- 0.01 in prednisolone-treated animals (P less than 0.01). In rabbits additionally given 1,25(OH)2D3, the mean value for bone density was further lowered (n.s.). It appears that 1,25(OH)2D3 exaggerates disuse osteoporosis and prednisolone osteoporosis and impairs fracture healing in rabbits. These results differ from what has been shown earlier with 1,25(OH)2D3 treatment in the rat.

Three months old male rats were fed a diet containing 0.3% calcium and 0.5% phosphate. Prednisolone was added to the diet at a dose of 1.5 mg a day and the effect of oral treatment with 0.5 micrograms 1 alpha OHD2 or 0.5 micrograms 1 alpha OHD3 was studied. After 6 weeks rats given prednisolone had a lower bone mass and bone density. The serum phosphate concentration was also lower. Rats given 1 alpha OHD3 had an increased serum calcium concentration even when simultaneously treated with prednisolone. 1 alpha OHD2 did not cause hypercalcaemia. The decrease in bone density caused by prednisolone was prevented by the administration of 1 alpha OHD2. Rats receiving 1 alpha OHD3 together with prednisolone still exhibited a lower bone density. Furthermore, 1 alpha OHD3 decreased bone mass in normal rats and caused a higher mean value of osteoclasts/area whereas 1 alpha OHD2 reduced the number of osteoclasts/area. The study indicates that 1 alpha OHD2 is an effective vitamin D analogue with a lower tendency to cause bone resorption.

Thirty-six women who had sustained soft-tissue injury after a simple fall were compared with age-matched controls who had suffered a fracture in a similar fall. Subjects aged 45-70 years who had suffered a fracture had significantly lower bone density in the proximal femur and lower grip strength than their controls. No differences in femoral bone density or grip strength were found between the two groups at ages over 70, but the women with fractures were on average of greater body weight than the no-fracture group. Bone mineral density declined more rapidly with age and was less closely correlated with body weight and time since menopause in the no-fracture group than among the women with a fracture. We conclude that the determinants of fracture vary with age; low bone density and low muscle strength are associated with fracture below the age of 70 but not at higher ages.

We measured the lumbar bone mineral of 19 cadavers (10 women, 9 men) by dual photon absorptiometry (DPA) and quantitative computed tomography (QCT). In addition, we determined the ultimate load and stress of each vertebra, and finally ash content and volumetric ash density of the vertebral body. We found that single energy QCT was inferior to DPA and dual energy QCT in the prediction of the ultimate load or stress of vertebrae (P less than 0.001). The ultimate stress was best predicted by using the dual energy QCT results (r = 0.71; SEE = 36.3 N/cm2) whereas the ultimate vertebral load was best predicted by using the DPA (BMC) results (r = 0.80; SEE = 740 N). If the QCT finding was multiplied with the surface area of the vertebral body it could be used to predict the ultimate load with good accuracy (r = 0.74; SEE = 841 N). All the above correlations were higher in women than in men. The frequency of vertebral compression fractures in the material was well correlated with the bone mineral findings. A nonlinear (third degree) relationship between mineral content and mechanical characteristics is proposed but within the area of measurement used in clinical practice a linear (first degree) equation is preferred.

Weanling vitamin D-deficient rats fed a high calcium, low phosphate diet were injected daily with 1 alpha-hydroxyergocalciferol or 1 alpha-hydroxycholecalciferol at doses of 2.5, 25 or 250 ng. Intestinal calcium and phosphate transport, serum phosphorus level, epiphyseal plate calcification, and percent femur ash increased as a function of the dose. Both compounds were equally effective in eliciting these responses demonstrating their equivalency as antirachitic compounds.

Intestinal calcium transport and renal calcium and phosphate excretion have been measured in normal and prednisolone-treated rats. Prednisolone treatment reduced intestinal calcium transport and increased phosphate excretion, causing a reduction in serum phosphate. Both 1 alpha-hydroxyvitamin D2 and 1 alpha-hydroxyvitamin D3 normalized phosphate excretion, whereas 1 alpha-hydroxyvitamin D3 was not fully effective in serum phosphate. Prednisolone treatment also caused a decreased bone density that was prevented both with 1 alpha-hydroxyvitamin D2 and 1 alpha-hydroxyvitamin D3. 1 alpha-hydroxyvitamin D2 appeared at least as effective as 1 alpha-hydroxyvitamin D3 in correcting the bone disturbance.

Adult male rats were fed a diet containing 0.15% calcium, 0.3% phosphorus, an either 100, 50, or 20 mg of prednisolone per kg of diet. All these levels of prednisolone led to osteopenia, decreased intestinal absorption of calcium, slightly lower serum calcium and phosphorus, and a decreased level of serum 1,25-dihydroxyvitamin D3. Exogenous parenteral 1,25-dihydroxyvitamin D3 corrected steroid-induced changes in serum calcium and phosphorus, but could not completely correct the low intestinal calcium transport; nor did it prevent the development of osteopenia. The prednisolone-induced osteopenia seems at least in part to be caused by impaired intestinal calcium transport. The impaired calcium transport may be the result of low levels of 1,25-dihydroxyvitamin D3 and a direct effect of presnisolone on the intestine.

Calcitonin and 1.25(OH)2D3 have opposite effects on the serum concentrations of Ca and P, as well as on bone resorption, and can be observed in the process of healing of standardized fracture in adult rats. The rats given 1.25(OH)2D3 had a stronger fracture callus and slightly less pronounced postfracture osteopenia. Calcitonin did not significantly influence the fracture healing but had a pronounced effect in preventing the osteopenia. The effects of 1.25(OH)2D3 are believed to be indirect, i.e., through the changes in the serum Ca X P product, whereas the osteopenia preventing action of calcitonin may come from direct effect on bone.