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Aims BoneMaster is a thin electrochemically applied hydroxyapatite (HA) coating for orthopaedic implants that is quickly resorbed during osseointegration. Early stabilization is a surrogacy marker of good survival of femoral stems. The hypothesis of this study was that a BoneMaster coating yields a fast early and lasting fixation of stems. Methods A total of 53 patients were randomized to be treated using Bi-Metric cementless femoral stems with either only a porous titanium plasma-sprayed coating (P group) or a porous titanium plasma-sprayed coating with an additional BoneMaster coating (PBM group). The patients were examined with radiostereometry until five years after surgery. Results At three months, the mean total translation (TT) was 0.95 mm (95% confidence interval (CI) 0.68 to 1.22) in the P group and 0.57 mm (95% CI 0.31 to 0.83) in the PBM group (p = 0.047). From two to five years, the TT increased by a mean of 0.14 mm (95% CI 0.03 to 0.25) more in the P group than in the PBM group (p = 0.021). In osteopenic patients (n = 20), the mean TT after three months was 1.61 mm (95% CI 1.03 to 2.20) in the P group and 0.73 mm (95% CI 0.25 to 1.21) in the PBM group (p = 0.023). After 60 months, the mean TT in osteopenic patients was 1.87 mm (95% CI 1.24 to 2.50) in the P group and 0.82 mm (95% CI 0.30 to 1.33) in the PBM group (p = 0.011). Conclusion There was less early and midterm migration of cementless stems with BoneMaster coating compared with those with only a porous titanium plasma-sprayed coating. Although a BoneMaster coating seems to be important for stem fixation, especially in osteopenic patients, further research is warranted . Cite this article: Bone Joint J 2022;104-B(6):647–656.

Introduction The aim of the study was to estimate recurrence rates, time to recurrence, and predisposing factors for recurrence of trigger finger when treated with corticosteroid (CS) injection as primary treatment. Materials and Methods In a retrospective chart review, we identified primary trigger fingers treated with CS injection as primary treatment. Affected hand and finger, recurrence, time to recurrence, duration of symptoms, secondary treatment type, and comorbidities were recorded. A total of 539 patients were included with a mean follow-up of 47.6 months Results In total, 330/539 (61%) recurrences were registered. Mean time to recurrence was 312 days. Increased risk of recurrence was seen after treatment of the third finger (relative risk [RR]: 1.22; 95% confidence interval [CI]: 1.06–1.39). Several comorbidities were associated with increased risk of recurrence: carpal tunnel syndrome (RR: 1.27; 95% CI: 1.07–1.52), thyroid disease (RR: 1.45; 95% CI: 1.15–1.83), or shoulder diseases (RR: 1.58; 95% CI: 1.36–1.83). Conclusion We found a recurrence rate after primary treatment of CS injection for trigger finger of 61%. Most recurrences happened within 2 years and we found treatment of third finger, carpal tunnel syndrome, shoulder, or thyroid disease to be associated with an increased risk of recurrence of symptoms.

Rapid wound closure is important after arthroplasty procedures to prevent postoperative complications. Platelets are rich in growth factors and leukocytes contribute to innate immunity. We hypothesized that topical leukocyte platelet-rich plasma (L-PRP) derived from the blood of patients would be beneficial to wound healing. In this randomized controlled trial, patients subjected to elective total hip arthroplasty (THA) were assigned by concealed allocation either L-PRP application onto the sutured fascia or no application (control) after the THA intervention. In addition, all patients received 1.5 g protein/kg, 5 g L-arginine, 500 mg vitamin C and 44 mg zinc daily over the 4-week postoperative period to obtain optimal nutrition. The primary endpoint was complete healing of the skin incision. The secondary endpoints were blood transfusions, length of hospital stay, pain and wound infections. Sixteen patients in the L-PRP group and 17 patients in the control group completed the trial. L-PRP treatment accelerated complete wound healing after 3 weeks (seven in the L-PRP group vs. zero in the control group, p = 0.003) and after 4 weeks (12 in the L-PRP group vs. six in the control group, p = 0.037). No postoperative superficial wound infections occurred within 4 weeks, and there were no significant differences in the other secondary outcomes. L-PRP generated in 10 sex-matched healthy volunteers revealed increased concentrations of platelets (5.8-fold) and leukocytes (2.3-fold) compared with those in whole blood. Furthermore, the concentration of keratinocyte mitogen epidermal growth factor in L-PRP (380 ± 130 pg/ml, mean ± SD) was higher (p < 0.001) than that in serum (130 ± 26 pg/ml). In conclusion, a single intraoperative local application of L-PRP promoted wound healing after THA, possibly mediated by EGF receptor agonists.

The purpose of this study was (1) to evaluate the results following thumb carpometacarpal (CMC) interposition arthroplasties with patient-reported outcomes (PRO) in a large prospective series, (2) ...

BACKGROUND: Several studies have confirmed a high rate of unexpected positive cultures (UPCs) after presumably aseptic revisions of shoulder arthroplasties; however, the impact on the outcome is still unclear. The purpose of this prospective study is to compare the patient-reported outcomes of standard revisions with and without the emergence of UPCs.METHODS: During a 3-year period, we included all patients who were revised for reasons other than suspicion of infection from two orthopedic centers. Five biopsies were obtained from every revision, and only cultures with the same bacteria in at least three biopsy specimens were classified as UPCs. All patients were assessed using the Oxford Shoulder Score (OSS) and range of motion preoperatively and after at least a two-year follow-up.RESULTS: In this study, 124 patients were included, with a median follow-up of 29 months (range 29-32), and UPCs emerged after 27 revisions (22%), with Cutibacterium acnes (C. acnes) accounting for 67% (18/27). At baseline, the OSS was 22 in both the culture-negative and UPC groups (p = 0.46). Then, at follow-up, the OSS was 37 in the culture-negative group and 35 in the UPC group (p = 0.91). The forward elevation increased significantly by 44° and 41° respectively in the two groups, but no statically significant difference between the culture-negative group and the UPC group was found (p = 0.66). In contrast, the external rotation was unchanged after the revision, and again, no difference in the change between the culture-negative and UPC groups (p = 0.54) was observed. Subgroup analyses stratified by different implant designs revealed equal patterns with no statistical differences in outcome.CONCLUSION: We did not find a difference in outcome after a presumed aseptic revision regardless of the emergence of UPCs. Similarly, we could not demonstrate that patients with UPCs presented with poorer function at baseline compared to culture-negative patients. The clinical relevance of UPCs thus requires further evaluation, especially in the case of C. acnes as a potential pathogenic contra merely colonizing microbe.

Background The large-diameter metal-on-metal hip prostheses were expected to have low wear and reduced dislocation rate compared to the traditional metal-on-polyethylene implants. We compare 2 such prostheses, the ReCap resurfacing implant and the M2a-Magnum stemmed implant, with the C2a ceramic-on-ceramic stemmed implant as to clinical performance, serum concentrations of prosthesis metals, and the durability of the implants in a randomized, controlled clinical trial at 7 years of follow-up. Methods All included patients had osteoarthritis. Preoperatively, the size of the implants was estimated from a magnetic resonance imaging (MRI) scan. Follow-up data included serum cobalt and chromium concentrations, Oxford and Harris Hip Scores, leg press and abduction force, 6-minute walk distance, WOMAC and SF-36 self-assessment scores, and from the 7th postoperative year also ultrasonography (US) examination of the soft tissue adjacent to the implant as well as MRI with metal artifact reduction sequence (MARS-MRI) when indicated. Results One hundred fifty-two hips in 146 patients were included. The serum cobalt and chromium concentrations were significantly higher for the 2 metal-on-metal prostheses than for the ceramic-on-ceramic, with the M2a-Magnum as the highest. No significant difference was found between the groups concerning physical performance measurements and scores as well as dislocations and prosthesis survival. Five revisions were done and concerned all groups, for reasons of pain, high serum cobalt and chromium concentrations, cystic fluid collection around the joint, and infection. Metal concentrations, US, and MARS-MRI contributed to the decision making regarding prosthesis revision. Conclusion Metal concentrations were significantly higher for the metal-on-metal prostheses than for the ceramic-on-ceramic. The clinical performance was good in all 3 prosthesis groups. Metal concentrations, US, and MARS-MRI findings were of use to identify hips needing revision. ID Number in ClinicalTrials.gov PRS: NCT00284674

Background: Shoulder periprosthetic joint infections (PJI) caused by low-virulent bacteria pose a diagnostic challenge. Combined labeled leukocyte (WBC) and technetium 99m sulfur colloid bone marrow imaging (WBC/BM) is considered the radionuclide imaging gold standard for diagnosing lower limb PJI. However, it is laborious and expensive to perform, and documentation on shoulder arthroplasties is lacking. This study investigated WBC/BM single-photon emission computed tomography-computed tomography diagnostic performance in shoulder PJI.Method: All patients with a failed arthroplasty referred to a highly specialized shoulder department were scheduled for a diagnostic program including a WBC/BM. If an arthroplasty was revised, biopsy specimens were obtained and cultured for 14 days. The diagnostic performance of WBC/BM imaging was determined using biopsy specimens as a reference.Results: Of the 49 patients who underwent a WBC/BM scan, 29 (59%) were revised. Infection was present in 11 patients, in whom 2 WBC/BM scans were true positive. The WBC/BM scan in 9 patients was false negative. The remaining 18 patients all had a true negative WBC/BM scan. WBC/BM showed a sensitivity 0.18 (95% confidence interval [CI], 0.00-0.41) and specificity 1.00 (95% CI, 1.00-1.00) in detecting shoulder PJI. The positive predictive value was 1.00 (95% CI, 1.00-1.00), and negative predictive value was 0.67 (95% CI, 0.49-0.84). No patients infected with Cutibacterium (formerly Propionibacterium) acnes resulted in a positive WBC/BM, nor had they preoperative or perioperative signs of infection.Conclusion: A positive WBC/BM was found only in patients with obvious PJI. Hence, the scan added nothing to the preoperative diagnosis. The WBC/BM single-photon emission computed tomography-computed tomography scan cannot be recommended as a screening procedure when evaluating failed shoulder arthroplasties for possible infection. (C) 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.

PURPOSE: Chronic low-grade periprosthetic joint infection (PJI) of a shoulder replacement can be challenging to diagnose. 18F-FDG PET/CT is suggested as a modality to diagnose lower-limb PJI, but no studies on shoulder replacements exist. The aim of this study was therefore to determine the diagnostic accuracy of 18F-FDG PET/CT in diagnosing chronic PJI of the shoulder.METHODS: Patients evaluated for a failed shoulder replacement during a 3-year period were prospectively included in the study. All patients underwent pre-operative 18F-FDG PET/CT, and were evaluated for signs of infection by three independent reviewers using shoulder-specific criteria. Interrater-agreement was calculated between the reviewers. If the patient had revision surgery, biopsy specimens were obtained and cultured with bacterial growth in the cultures serving as gold standard of infection.RESULTS: A total of 86 patients were included in the study. Nine patients were 18F-FDG PET/CT positive for infection, with only three true positive. Using the gold standard, infection was diagnosed after revision surgery in 22 cases. All infections were chronic and caused by low-virulent microbes. The sensitivity of 18F-FDG PET/CT was 0.14 95% CI (0.03-0.36), specificity 0.91 95% CI (0.81-0.97), positive predictive value was 0.40 95% CI (0.15-0.71) and negative predictive value 0.71 95% CI (0.67-0.75). The inter-observer agreement was 0.56 (Fleiss' kappa), indicating moderate agreement of the visual FDG-PET evaluation using the shoulder-specific criteria.CONCLUSION: 18F-FDG PET/CT has poor diagnostic accuracy in diagnosing low-grade PJI of the shoulder. 18F-FDG PET/CT cannot be recommended as a part of the routine preoperative workup to diagnose low-grade infection of a shoulder replacement.

Purpose To compare 4 different bearings in total hip arthroplasty (THA) in a randomised controlled clinical study on clinical performance. Methods 393 patients with osteoarthritis of the hip or avascular necrosis were included and allocated to 1 of the head-and-cup couples zirconia-on-polyethylene (group A), metal-on-metal (group B), zirconia-on-polyethylene with the liner moulded into the shell (group C), or alumina-on-alumina (group D). In the individual case the surgeon could choose other implants if indicated. Results 299 patients were operated with the allocated prosthesis. The estimated cumulated prosthesis survival percentages and 95% confidence interval after 10 years were: group A 84.6 (75.8-93.4); group B 95.0 (89.5-100); group C 93.2 (86.7-99.7); group D 66.1 (54.5-77.7). The patients' physical function was significantly improved and remained equally good in all 4 groups, however slightly declining with ageing. The luxation rate was initially high, and equal between the groups, but was reduced by improving the surgical procedure introducing capsule repair by reinsertion of the short external hip rotators. Conclusions The metal-on-metal or zirconia-on-polyethylene prostheses had high 10-year survival percentages. The longevity of these bearing couples by themselves was not related to the combination of materials. The zirconia-on-polyethylene prosthesis with the liner mounted peroperatively possibly exhibited cases of backside wear which the corresponding bearing couple with moulded polyethylene (Asian) did not. The alumina-on-alumina bearing performed poorly - it was redesigned after our study initiation and later withdrawn from the market.

Background and purpose Intermittent administration of parathyroid hormone (PTH) has an anabolic effect on bone, as confirmed in human osteoporosis studies, distraction osteogenesis, and fracture healing. PTH in rat models leads to improved fixation of implants in low-density bone or screw insertion transcortically. Material and methods We examined the effect of human PTH (1–34) on the cancellous osseointegration of unloaded implants inserted press-fit in intact bone of higher animal species. 20 dogs were randomized to treatment with human PTH (1–34), 5 μg/kg/day subcutaneously, or placebo for 4 weeks starting on the day after insertion of a cylindrical porous coated plasma-sprayed titanium alloy implant in the proximal metaphyseal cancellous bone of tibia. Osseointegration was evaluated by histomorphometry and fixation by push-out test to failure. Results Surface fraction of woven bone at the implant interface was statistically significantly higher in the PTH group by 1.4 fold with (median (interquartile ...

The goal of osseointegration of orthopedic and dental implants is the rapid achievement of a mechanically stable and long lasting fixation between living bone and the implant surface. In total joint replacements of cementless designs, coatings of calcium phosphates were introduced as a means of improving the fixation of implants. Of these, hydroxyapatite (HA) is the most widely used and most extensively investigated. HA is highly osseoconductive, and the positive effect is well documented in both basic and long-term clinical research [1–6]. This chapter describes experimental and clinical studies evaluating bone-implant fixation with HA coatings.

The effects of intravenous administration of 1 alpha-hydroxycholecalciferol [1 alpha (OH)D3] in combination with CaCO3 and 'low-calcium dialysis' (1.25 mmol/l) on plasma (p) parathyroid hormone (PTH) and biochemical bone markers (osteocalcin, alkaline phosphatase, procollagen type 1 c-terminal extension peptide) were examined in 54 patients on chronic hemodialysis with either normal or elevated PTH. Increasing doses of 1 alpha (OH)D3 were administered intravenously under careful control of p-Ca2+ and inorganic phosphate. Blood samples were obtained 1 week before the start of treatment and then every 2nd week. 20 patients with initially normal PTH levels (23.5 +/- 4.17 pg/ml) and 34 patients with initially elevated PTH levels (301 +/- 45 pg/ml) were followed for up to 88 weeks. The present investigation: demonstrated: (1) 'Low-calcium hemodialysis' (1.25 mmol/l) made it possible to use larger doses of CaCO3 and to reduce the doses of an aluminium-containing oral phosphate binder. A decrease in p-Ca2+ during dialysis was induced, and special care had to focus on the compliance to CaCO3, in order not to aggravate the secondary hyperparathyroidism. (2) The combination of 'low-calcium hemodialysis', CaCO3, and pulse intravenous 1 alpha (OH)D3 prevented the development of secondary hyperparathyroidism in patients with normal PTH levels and induced a long-term suppression of p-PTH (106 +/- 25 pg/ml, 88 weeks) in the patients with secondary hyperparathyroidism. By careful monitoring, severe hypercalcemia and hyperphosphatemia were avoided. There were no indications, clinically or biochemically, of development of adynamic bone disease. (3) Bone lesions were healed and a decrease of the bone mineral content in lumbar spine and femoral neck of patients with both normal and elevated PTH levels prevented. (4) The present results may suggest that PTH might be of influence on that regulation of procollagen type 1 c-terminal extension peptide.

The metabolism of added N-terminal and C-terminal synthetic human PTH (synhPTH) fragments was studied in isolated perfused rat livers and in filtering and nonfiltering kidneys. Initial concentrations: synhPTH-(1-34), 14 pmol/liter, synhPTH-(39-84) 85 pmol/liter, synhPTH-(1-84) 3 pmol/liter, or 1000 pmol/liter of each fragment and intact PTH. Clearances were measured by assays specific for intact PTH, N-terminal, midmolecule, and C-terminal immunoreactive PTH. Metabolism of the added PTH into smaller circulating fragments was analyzed by HPLC. The clearance of synhPTH-(1-34) in the filtering kidneys was not significantly different from the clearance of synhPTH-(39-84) and inulin, and HPLC demonstrated no metabolism of synhPTH-(1-34) or synhPTH-(39-84) in the kidneys. The livers did not clear synhPTH-(39-84), while the clearance of synhPTH-(1-34) was significant (P < 0.005). HPLC demonstrated no metabolism of synhPTH-(39-84) by the livers, but extensive metabolism of synhPTH-(1-34). The livers cleared synhPTH-(1-34) significantly (P < 0.05) faster than synhPTH-(1-84). In conclusion, the kidneys cleared N-terminal PTH fragments at the same rate as C-terminal fragments mainly by filtration. The livers cleared N-terminal fragments faster than intact PTH, but did not clear C-terminal fragments. This differential hepatic clearance may play a major role in maintaining the differences between the circulating levels of N-terminal and C-terminal immunoreactive PTH.

Primary joint replacements generally function well with excellent clinical results. However, failure rates for young patients are still high and increasing in number. The longterm survival of an uncemented prosthesis is influenced by multiple factors depending on host physiology as well as properties of implanted material, initial mechanical stability, early osseointegration, and the surrounding bone. Parathyroid hormone is the principal regulator of calcium homeostasis and involved in the control of bone remodelling. Parathyroid hormone administered intermittently increases bone formation and mass by osteoblast stimulation. Early osseointegration and implant fixation could potentially be enhanced with adjuvant parathyroid hormone treatment. The aim of the studies in this PhD thesis was to determine if implant fixation of experimental implants can be improved with adjuvant intermittent administration of parathyroid hormone.All studies used an experimental canine model of early implant fixation inserting porous coated titanium alloy implants with no weight bearing in a bed of cancellous bone. The study design was un-paired. Test animals were randomised to PTH (1-34) 5 μm/kg daily for 4 weeks. Implant fixation was defined by mechanical stability and osseointegration. Study I investigated the effect of parathyroid hormone on implant fixation of implants inserted press fit with surrounding bone in the proximal tibia of 20 canines. Histomorphometric analysis showed increased amount of new bone in contact with the implant. No improvement was observed in the surrounding bone. PTH did not increase mechanical fixation in pushout test. Study II investigated the effect of parathyroid hormone on implant fixation of implants surrounded by a critical 1 mm gap. Implants where inserted in the tibia of 20 canines. Bone density was increased in the inner gap and outer gap with PTH treatment. Bone at implant interface improved with PTH but did not achieve significance. Push-out testing showed that PTH Increased mechanical implant fixation in shear stiffness and total energy absorption. Shear strength was not significantly increased. Study III investigated the effect on implant fixation of implants surrounded by a 2.5 mm gap in which morsellised allograft was impacted. Implants were inserted in 20 Canines in the humerus. Histomorphometric analysis showed that PTH increased the amount of new bone within the gap, but not in contact the implant. There were no differences in amount of allograft. The push-out testing showed no differences in mechanical parameters.The studies in this PhD thesis demonstrated that parathyroid hormone increases bone healing around implants in situations of insertion in press-fit or in more challenging environments of empty and grafted gaps. Early fixation was increased in implants with gaps, in which pure gap bone stimulation improved fixation. This warrants further preclinical studies.

Parathyroid hormone (PTH) administered intermittently is a bone-building peptide. In joint replacements, implants are unavoidably surrounded by gaps despite meticulous surgical technique and osseointegration is challenging. We examined the effect of human PTH(1-34) on implant fixation in an experimental gap model. We inserted cylindrical (10 × 6 mm) porous coated titanium alloy implants in a concentric 1-mm gap in normal cancellous bone of proximal tibia in 20 canines. Animals were randomized to treatment with PTH(1-34) 5 μg/kg daily. After 4 weeks, fixation was evaluated by histomorphometry and push-out test. Bone volume was increased significantly in the gap. In the outer gap (500 μm), the bone volume fraction median (interquartile range) was 27% (20-37%) for PTH and 10% (6-14%) for control. In the inner gap, the bone volume fraction was 33% (26-36%) for PTH and 13% (11-18%) for control. At the implant interface, the bone fraction improved with 16% (11-20%) for PTH and 10% (7-12%) (P = 0.07) for control. Mechanical implant fixation was improved for implants exposed to PTH. For PTH, median (interquartile range) shear stiffness was significantly higher (PTH 17.4 [12.7-39.7] MPa/mm and control 8.8 [3.3-12.4] MPa/mm) (P

The effect of uremia on hepatic metabolism of aldosterone was studied in the isolated perfused liver of female Wistar rats. Uremia was induced by five-sixths' partial nephrectomy 4 weeks before experiments. Isolated livers of normal and uremic rats were perfused at a constant flow rate with a hemoglobin-free medium, to which 4-14C-d-aldosterone was added at 3 nmol/L. Aldosterone was analyzed by radioimmunoassay (RIA) and 4-14C-d-aldosterone radiometabolites in perfusate and bile were assayed by high-performance liquid chromatography (HPLC). Uremic rats had a 10% lower body weight (P < .01) and increased plasma urea, creatinine, and parathyroid hormone (PTH) levels (258%, 200%, and 208%, respectively; P < .01–.001). Blood pressure and plasma K+, Na+, and aldosterone levels were similar. Plasma renin activity was suppressed by 68% in uremic rats (P < .001). Liver wet weight and hepatic function were similar in livers of both groups of rats. Hepatic elimination of aldosterone was compatible with a first-order kinetics. Hepatic clearance of aldosterone per liver and per gram liver was similar; however, when expressed per 100 g rat body weight, a 21% higher value was observed in uremic rats (11.6 ± 1.8 mL/min) compared with normal rats (9.6 ± 1.5 mL/min, P < .01). Polar aldosterone radiometabolites accumulated in the perfusate to approximately 40% of the initial 14C added at 15 minutes, and were eliminated in bile at a similar rate in both groups. No qualitative difference was found in the pattern of radiometabolites of aldosterone in perfusate and bile. Thus, despite a relatively increased capacity of hepatic aldosterone metabolism, chronic uremia in the rat did not specifically affect hepatic metabolism of aldosterone.

Skeletal bone consists of hydroxyapatite (HA) [Ca(10)(PO(4))(6)(OH)(2)] and collagen type I, both of which are osseoconductive. The goal of osseointegration of orthopedic and dental implants is the rapid achievement of a mechanically stable long-lasting fixation between bone and an implant surface. In this study, we evaluated the mechanical fixation and tissue distribution surrounding implants coated with three surfaces: plasma-sprayed HA coating, thinner coating of electrochemical-assisted deposition of HA, and an identical thin coating with a top layer of mineralized collagen. Uncoated plasma-sprayed titanium (Ti-6Al-4V) served as negative control. The electrochemical-assisted deposition was performed near physiological conditions. We used a canine experimental joint replacement model with four cylindrical implants (one of each treatment group) inserted in the humeri cancellous metaphyseal bone in a 1 mm gap. Observation time was 4 weeks. The mechanical fixation was quantified by push-out test to failure, and the peri-implant tissue formation by histomorphometric evaluation. HA coatings deposited by plasma spray technique or electrochemically, increased the mechanical fixation and bone ongrowth, but there was no statistical difference between the individual HA applications. Addition of collagen to the mineralized phase of the coating to create a more bone natural surface did not improve the osseoconductive effect of HA.

Udgivelsesdato: 2009-Dec The objective of this study was to directly measure the radiation exposure to the orthopaedic surgeon and to measure dose points to the surgeon's fingers, thyroid gland, and forehead during intraoperative fluoroscopy in periacetabular osteotomy (PAO). In a series of 23 consecutive periacetabular osteotomy procedures, exposure monitoring was carried out using thermo luminescent dosimeters. The effective dose received by the operating surgeon was 0.008 mSv per operation which adds up to a yearly dose of 0.64 mSv from PAO. The median point equivalent dose (mSv) exposure under PAO was 0.009 for the forehead and thyroid gland, 0.045 for the right index finger, and 0.039 for the left index finger. The effective estimated yearly dose received by the operating surgeon was very low. Wearing a lead collar reduces radiation exposure to the thyroid gland while the lead gloves did not protect the surgeon's fingers.

Circulating levels of calciotropic hormones were measured during one year of treatment with either 200 IU of salmon calcitonin daily or placebo as a nasal spray in 20 postmenopausal women with a former Colles' fracture. A supplement of 0.5 gram elemental calcium was given to all participants. Serum levels of parathyroid hormone and human calcitonin were determined with radioimmunoassays, and serum levels of vitamin D metabolites were determined with protein binding assays. We did not find any significant differences between the two groups with respect to serum levels of calciotropic hormones. In the salmon calcitonin treated group there was a tendency towards a small decrease in serum levels of human calcitonin and an increase in serum levels of calcitriol. Our results suggest that treatment with 200 IU of salmon calcitonin daily as a nasal spray does not markedly affect fasting serum levels of parathyroid hormone, human calcitonin, and vitamin D metabolitis.

Metabolism of parathyroid hormone in isolated perfused rat kidney and liver combined. Metabolism of synthetic, intact, human parathyroid hormone (PTH) 10-9 M was studied in a new experimental model using the isolated perfused rat kidney and liver combined. The combined organs cleared intact PTH significantly faster than the single kidneys (P < 0.02) or livers (P < 0.02), but not faster than the sum of the clearances in the single organs. The kidneys cleared intact PTH without accumulation of NH2-terminal, mid-molecule or COOH-terminal iPTH, and high-performance liquid chromatography (HPLC) studies did not reveal any PTH fragments. The livers cleared mid-molecule and COOH-terminal iPTH significantly slower {P < 0.002) than intact PTH, and HPLC demonstrated generation of mid-molecule and COOH-terminal PTH fragments. The combined organs accumulated significantly less mid-molecule (P < 0.001) and COOH-terminal (P < 0.03) iPTH than the single livers, and HPLC demonstrated mid-molecule peaks that were smaller but not qualitatively different. In conclusion, the predominance of COOH-terminal PTH fragments in plasma may be maintained by differential clearance mainly in the liver, excessive accumulation being prevented by filtration in the kidneys.

The metabolism of synthetic human PTH [PTH-(1-84)] 10(-9) M was studied in isolated rat kidneys and livers, perfused at a calcium concentration of 1 mM or 4 mM. Clearances were measured by an assay specific for intact PTH, and by assays specific for NH2-terminal, mid-molecule, and COOH-terminal immunoreactive PTH (iPTH). Production of PTH fragments was analyzed by HPLC. The kidneys cleared PTH mainly by filtration. The glomerular filtration rate was not lower at 4 mM calcium than at 1 mM calcium, and no significant differences were found between the clearance of PTH at 4 mM and at 1 mM calcium. At 1 mM calcium the kidneys cleared intact PTH without release of detectable fragments. At 4 mM calcium there was significant (P less than 0.05) accumulation of mid-molecule and COOH-terminal iPTH in the perfusate. Both at low and at high calcium the livers cleared NH2-terminal iPTH at the same rate as intact PTH, whereas mid-molecule and COOH-terminal iPTH was cleared significantly (P less than 0.005) slower. In the livers, metabolic clearance of PTH was 60% faster at 4 mM calcium than at 1 mM calcium (P less than 0.001). Assuming that the hepatic metabolism of PTH represents degradation of the biologically active hormone and hormone fragments, rather than activation of the hormone, the present results suggest a homeostatic control of PTH degradation in the liver to enhance inactivation of the hormone at high serum levels of calcium.

Brandi L, Daugaard H, Egsmose C, Tvedegaard E, Kjaerulff Nielsen P, Olgaard K (Medical Department P, Division of Nephrology, Rigshospitalet, University of Copenhagen, Denmark). Intermittent intravenous followed by intermittent oral 1α(OH)D3 treatment of secondary hyperparathyroidism in uraemia. J Intern Med 1996; 239: 353–60. Objectives. To examine whether intermittent oral 1α(OH)D3 treatment of patients on haemodialysis with secondary hyperparathyroidism (HPT) was able to maintain the marked suppression of PTH, which previously had been induced by an intermittent intravenous administration of 1α(OH)D3. Simultaneously, the effect of the different routes of administration of 1α(OH)D3 on the circulating levels of N-and C-terminal PTH fragments was measured. Design. An open study of patients on chronic haemodialysis. Setting. Renal division, Rigshospitalet, Copenhagen, Denmark. Subjects. A total of 26 patients started and five patients completed the total protocol. Interventions. The treatment protocol was divided into three parts: (i) 1α(OH)D3 administered intravenously for >300 days; then (ii) 1α(OH)D3 administered orally for 100 days, followed by (iii) 1α(OH)D3 administered intravenously again for another 100 days. 1α(OH)D3 was given three times a week at the end of each dialysis. Main outcome measures. Intact PTH, N- and C-terminal PTH. Results. Intact PTH levels were significantly (P

The aim of the present study was to assess the long-term function of autotransplanted parathyroid tissue in patients with chronic renal disease. We examined the medical records of a consecutive series of 21 patients with chronic renal failure, who had undergone total parathyroidectomy with autotransplantation. During the time of follow-up, on average 79 months, one patient developed graft-dependent recurrent hyperparathyroidism and one patient suffered from persistent hypoparathyroidism. Nine of the patients were available for a clinical study. In these patients we measured the plasma concentration of intact PTH in blood from the arm contralateral to the graft-bearing arm at rest and during a short-lasting ischaemic blockade of the graft site from the circulating blood. At rest all nine patients had parathyroid hormone (PTH) values within the normal range. The ischaemic blockade produced a marked reduction in the plasma concentration of intact PTH in eight of the patients indicating well functioning autografts. Prior to the examination the patient with recurrent hyperparathyroidism had undergone resection of the autograft. In this patient, ischaemia of the former graft site did not cause any change in the concentration of PTH indicating normally functioning residual parathyroid tissue in the neck. Thus, the ischaemic blockade manoeuvre seems suitable for the assessment of autografted parathyroid tissue. Our results indicate that total parathyroidectomy with autotransplantation provides a rational alternative to the surgical treatment of secondary hyperparathyroidism.

Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood and urine samples were collected for 26 hours. There was a significant decrease in serum ionized calcium with a nadir 4 hours after administration of nasal SCT accompanied by a significant increase in serum parathyroid hormone (P = 0.01) and serum calcitriol (P = 0.04). Nasal SCT did not reduce urinary hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered significantly 2 hours after administration of nasal SCT and throughout the first 24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis, urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11.7 (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide of type 1 procollagen. The results indicate that nasal SCT given as a single dose provokes a modest decrease in bone resorption lasting several hours, but leaves bone formation unaffected.

The effect of glucocorticoid deficiency and excess on the extraadrenal metabolism of D-[4-14C]aldosterone (at 4 nM) was studied by radioimmunoassay and by high-performance liquid chromatography in the isolated perfused liver and kidney of adult Wistar rats. Bilateral adrenalectomy was performed 3 weeks before experiments. In nonadrenalectomized rats, 0.3 mg/kg/day dexamethasone was continuously infused subcutaneously for 1 week before experiments. Adrenalectomy did not affect hepatic or renal metabolism of aldosterone. Dexamethasone treatment did not change the renal handling of aldosterone. However, the hepatic clearance of aldosterone was 19% lower (P less than 0.05) in livers of dexamethasone treated rats than in livers of normal rats. After 5 minutes, perfusate [4-14C]aldosterone metabolites were lower in livers of dexamethasone-treated than in livers of normal rats (P less than 0.05). Similar perfusate levels were then obtained. Radiometabolite peaks with similar relative retention times were found in the hepatic perfusate of all groups. However, the ratio between circulating polar metabolites of aldosterone and the metabolites less polar than tetrahydroaldosterone, after 5 and 15 minutes, was highest in livers of dexamethasone-treated rats. Biliary elimination of 14C was similar in all groups. Significant amounts of conjugated tetrahydroaldosterone were only excreted in the bile of dexamethasone-treated rats. In conclusion, glucocorticoid excess reduced the hepatic clearance of aldosterone and changed the pattern of the hepatic metabolites of aldosterone both in circulation and in bile.

The metabolism of aldosterone (Aldo) at 4 nM was studied by radioimmunoassay and by high-performance liquid chromatography in isolated perfused liver (IPL), isolated perfused kidney (IPK), and combined isolated perfused liver and kidney (CIPLK) of male Wistar rats. Effect of D[4-(14)C]aldosterone (D [4-(14)C]Aldo) on the function of IPK of intact and adrenalectomized (ADX) rats was also studied. Aldo clearance in the liver was most important, 16.3 +/- 1.7 ml/min. In IPK, the total clearance of Aldo was 0.27 +/- 0.36 ml/min (39% of the glomerular filtration rate) (GFR). Fractional excretion (FE) of Aldo was 16 +/- 8%. Metabolic clearance of Aldo was (0.21 +/- 0.23 ml/min), 78% of total renal clearance. In CIPLK, the kidney inhibited hepatic clearance of Aldo by 23% when compared with IPL (P less than 0.05). Hepatic Aldo metabolites were predominantly eliminated by biliary excretion of polar metabolites. Several hepatic polar metabolites and tetrahydroaldosterone (THA) accumulated in perfusate and were excreted in the urine in a similar pattern. After hydrolysis of the polar metabolites, some coeluated with THA and dihydroaldosterone (DHA), whereas other metabolites remained more polar than Aldo. Without addition of Aldo, in IPK of ADX rats FENa was higher (P less than 0.01), and FEK was lower (P less than 0.01), resulting in three- to fourfold higher urinary Na-K ratio (P less than 0.01) when compared with IPK and CIPLK of intact rats. In IPK of ADX rats with Aldo in perfusate, only FEK was restored. Addition of Aldo to IPK of intact rats had no effect. However, only in CIPLK, addition of Aldo resulted in an increasing kaliuresis in three subsequent periods of 30 min (0.56-0.95, P less than 0.01). Thus the hepatic metabolites of Aldo could in part mediate the kaliuretic effect of Aldo.

The effect of intravenous 1 alpha(OH)D3 on circulating intact parathyroid hormone (PTH) and COOH-terminal immunoreactive PTH was examined in 21 patients on chronic hemodialysis. The patients were treated for 3 months with increasing doses of 1 alpha(OH)D3 under careful control of serum Ca2+. 1 alpha(OH)D3 was given intravenously at doses of up to 4 micrograms three times a week, and blood samples were obtained every week, including 1 week before treatment (basal control). No patients were treated with oral vitamin D metabolites. At the end of the study intact PTH levels were reduced by an average of 67 +/- 6%, and COOH-terminal immunoreactive PTH levels were reduced by 35 +/- 6%. Serum Ca2+ was kept within normal levels, but showed a slight increase from 1.17 to 1.30 mmol/l. An effect of calcium on PTH secretion could not be excluded, but an effect of 1 alpha(OH)D3, independent of serum Ca2+ was also found. This effect may be mediated by 1,25(OH)2D3, assuming a large capacity of the 25-hydroxylase in the liver to convert 1 alpha(OH)D3 to 1,25(OH)2D3. Also, the parathyroid glands may possess receptors for 1 alpha(OH)D3 with an effect similar to that established for the 1,25(OH)2D3 receptors. Thus, although the exact mechanisms of the action of 1 alpha(OH)D3 have not yet been completely clarified, it is concluded that intravenous administration of 1 alpha(OH)D3 may be of benefit in the treatment of secondary hyperparathyroidism of uremia.

Bone Gla protein (BGP, osteocalcin) is a marker of bone formation. We present a novel enzyme-linked immunosorbent assay for measuring BGP in plasma and serum. The antibody used was raised in rabbits following immunisation with highly purified bovine BGP conjugated with keyhole limpet hemocyanin. The binding of the antibody to BGP was calcium-dependent. The sensitivity, inaccuracy, and imprecision of the assay equal or exceed existing radioimmunoassays, and the present assay is less tedious. Plasma BGP in 249 healthy adults, aged from 20 to 93 yr, was 8.3 +/- 6.6 micrograms/l (mean +/- 2 SD). A significant decrease was seen in both sexes from the third to the forth decade of life. A subsequent significant increase was seen with age in women. but not in men. Plasma BGP was significantly higher in young men than in young women, and significantly higher in elderly women than in elderly men. Values were in the same range as those found with existing radioimmunoassays.

In previous clinical investigations we found a stimulatory effect of the presence of hyperparathyroidism on the Ca++ induced secretion of aldosterone and vasopressin. The present investigation, therefore, examined the possible effect of PTH on the Ca++ mediated aldosterone secretion from purified rat zona glomerulosa cells.

Intestinal calcium-binding protein (CaBP) (molecular weight 10,000) was measured by a specific enzyme-linked immunoadsorbent assay in duodenal biopsies of 94 patients (aged 20-89 years). The patients were examined for complaints of upper abdominal dyspepsia, but no significant pathology was found by gastroduodenoscopy. The median amount of CaBP in duodenal biopsies was 6.0 micrograms/mg of cytosolic protein with a coefficient of variation of 0.6. No change in the amount of CaBP per mg of cytosolic protein was observed with age. A significant correlation (P less than 0.001) was found between the concentration of CaBP and s-1,25-dihydroxyvitamin D (1,25(OH)2D). The amount of CaBP per mg of cytosolic protein did not correlate with immunoreactive parathyroid hormone in serum, and no relation between CaBP and the specific activity of alkaline phosphatase of the mucosal biopsies was found. The results of the present study show a wide variation in the amount of the 10 kDa CaBP in duodenal biopsies of humans and no change with age. Further, a correlation between s-1,25(OH)2D and CaBP was found.

Metabolism of synthetic human parathyroid hormone (PTH) 2 X 10(-10) to 5 X 10(-9) M was studied in 16 isolated perfused rat kidneys and 12 isolated perfused rat livers. Organ clearances were measured by assays specific for intact PTH. Production of fragments was analyzed by high-performance liquid chromatography (HPLC) and radioimmunoassays specific for NH2-terminal, midmolecule, and COOH-terminal PTH. The livers cleared intact PTH and NH2-terminal immunoreactive PTH (iPTH) at the same rate. Midmolecule iPTH was cleared significantly (P less than 0.001) slower, as was COOH-terminal iPTH (P less than 0.005), and HPLC studies demonstrated production of midmolecule/COOH-terminal PTH fragments, while no NH2-terminal fragments were found. Clearance in the kidneys of intact PTH and of NH2-terminal, midmolecule, and COOH-terminal iPTH was not significantly different from clearance of inulin. No clearance of intact PTH was found in nonfiltering kidneys. HPLC studies did not demonstrate release of any PTH fragments from the kidneys. In conclusion, the liver was not selective for intact PTH, and differential hepatic clearance, possibly together with direct glandular secretion, may contribute to the predominance of COOH-terminal PTH fragments in plasma.

Objective To evaluate risk/benefit of various continuous ambulatory peritoneal dialysis (CAPD) dialysate calcium concentrations. Data Sources A review of the literature on the effects of various CAPD dialysate Ca concentrations on plasma Ca, plasma phosphate, plasma parathyroid hormone (PTH), doses of calcium carbonate, doses of vitamin D analogs, and requirements of aluminum-containing phosphate binders. Study Selection Eleven studies of nonselected CAPD patients, and 13 studies of CAPD patients with hypercalcemia were reviewed. Results In nonselected CAPD patients, treatment with a reduced dialysate Ca concentration (1.00, 1.25, or 1.35 mmol/L) improved the tolerance to calcium carbonate and/or vitamin D metabolites and reduced the need for Al-containing phosphate binders. When using dialysate Ca 1.25 or 1.35 mmol/L, the initial decrease of plasma Ca and increase of PTH could easily be reversed with an immediate adjustment of the treatment. After 3 months, stable plasma Ca and PTH levels could be maintained using only monthly investigations. In patients with hypercalcemia and elevated PTH levels, treatment with dialysate Ca concentrations below 1.25 mmol/L implied a considerable risk for the progression of secondary hyperparathyroidism. When hypercalcemia was present in combination with suppressed PTH levels, a controlled increase of PTH could be obtained with a temporary discontinuation of vitamin D and/or a reduction of calcium carbonate treatment in combination with a dialysate Ca concentration of 1.25 or 1.35 mmol/L. Conclusion Most CAPD patients can be treated effectively and safely with a reduced dialysate Ca concentration of 1.35 or 1.25 mmol/L. Treatment with dialysate Ca concentrations below 1.25 mmol/L should not be used. A small fraction of patients with persistent hypocalcemia need treatment with high dialysate Ca, such as 1.75 mmol/L.