Urinary concentration of collagen metabolites in endoprosthesis loosening

Aseptic loosening is the most common long-term complication in arthroplasty. Loosening is in every case associated with bone resorption at the interface that leads to bone defects and complicates the revision. The diagnosis of aseptic loosening is based on clinical and radiological evaluation. Especially in clinically asymptomatic cases an early diagnosis with these methods is difficult. In our study we wanted to evaluate the diagnostic value of biochemical markers of the bone resorption in aseptic loosening. We compared 58 patients with proven implant loosening during surgery with 67 patients without clinical or radiological signs of loosening. We measured the crosslinks pyridinoline and hydroxypyridinoline in urine samples. In contrast to Schneider et al. [increased urinary crosslink levels in aseptic loosening of total hip arthroplasty, J. Arthroplasty 1995; 13 (6): 687-692] we found no significant differences between loose and asymptomatic hip or knee prosthesis. Also no correlation between the size of the acetabular defects of loose hip implants and the urinary crosslink excretion was measurable. Our results show no or only little diagnostic value of the urinary crosslinks pyridinoline and deoxypyridinoline in aseptic loosening of total hip and knee arthroplasty.     

Biochemical markers of bone turnover in aseptic loosening in hip arthroplasty

The aim of this study was to determine the diagnostic value of systemic biochemical markers of bone turnover in aseptic loosening in hip arthroplasty, namely the urine levels of three bone resorption peptides – crosslinked n-telopeptides (NTX), c-telopeptides (CTX I) and deoxypyridinoline (DPD). We compared 52 patients with surgically proven component loosening with 52 patients without clinical or radiological signs of endoprosthetic loosening and 52 healthy individuals. All three markers were measured using commercially available enzyme-linked immunoassays. We found significantly increased levels of DPD in the loosening group (p < 0.05), but there was no significant difference between the loosening group and the two reference groups for the other two markers tested. Our data suggest that DPD can be used as an additional tool in the diagnosis of aseptic loosening in hip arthroplasty but CTX I and NTX have no predictive value in this context.

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Résumé  Le but de cette étude est de déterminer la valeur diagnostic de marqueurs bio-chimiques dans le descellement aseptique des prothèses totales de hanche, en mesurant un certain nombre peptides issus de la résorption osseuse (crosslinked n-telpeptides [NTX], c-telpepetides [CTX I] et deoxypyridinoline [DPD]. nous avons comparé les paramètres de 52 individus présentant un descellement aseptique à 52 individus sains. Tous les paramètres ont été mesurés par la méthode ELISA. nous avons trouvé une augmentation significative des DPD dans le groupe prothèses descellées (p < 0.05). Il n’y a pas de différence significative entre les deux groupes pour les autres marqueurs. nous suggérons que la DPD peut être utilisée comme un marqueur additionnel du diagnostic des descellements aseptiques des prothèses totales de hanche par contre, il n’y a pas de valeurs prédictives pour les marqueurs CTX1 et NTX.

     

Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures.

To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals.     

Synovial fluid from loose hip arthroplasties inhibits human osteoblasts

Aseptic loosening of prosthetic components in patients who have undergone total hip arthroplasty is a major clinical problem. Earlier studies on this topic have focused mainly on different aspects of bone resorption. The current study investigated the influence of synovial fluid from patients who underwent revision surgery because of aseptic loosening and synovial fluid from patients with osteoarthritis on the proliferation of primary cultures of human osteoblasts. Incubation of cells with 10% synovial fluid from patients who had revision surgery significantly inhibited [3H]thymidine incorporation into deoxyribonucleic acid in human osteoblasts compared with control conditions, whereas 10% synovial fluid from patients with osteoarthritis had a significant stimulatory effect. These findings correlate well with clinical features seen in these diseases, such as increased net bone resorption around the prosthesis in patients with loosening, and increased periarticular bone formation in patients with osteoarthritis.     

Bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis, seventy eight revisions using bone allografts with or without metal reinforcements

Purpose

The aim of the study was to assess bone graft incorporation after revision hip arthroplasty in patients with rheumatoid arthritis (RA).

Methods

We report an acetabular reconstruction using impacted, morselized, frozen, radiation sterilized bone allografts in 71 patients suffering from RA. There were sixty-six women and five men at a mean age of 57.5 years. Reconstruction was performed in 78 revision total hip arthroplasties (THAs) for aseptic loosening of acetabular component. The mean follow-up was five years and four months. In 38 cases, a revision was done with use of reinforcement devices.

Results

In four revised hips (10 %) without reinforcement implants, resorption of the allografts was noticed. All Mueller rings and 50 % of unscrews cages (Link, Howmedica) were revised because of aseptic loosening and bone graft resorption. In all of 17 hips with the Burch-Schneider cage, no measurable migration or bone allografts resorption occurred. There were no major general complications.

Conclusions

Acetabular reconstruction with use of morselized, frozen, radiation sterilized bone allografts and the Burch-Schneider cage can be highly successful in managing massive deficiency of acetabular bone stock in revision hip arthroplasty in RA patients.     

Monitoring alendronate therapy for osteoporosis.

Alendronate is an antiresorptive therapy for osteoporosis and results in a decrease in bone turnover. To choose the optimal measurement for monitoring this therapy, the size of the change needs to be compared with the variability of the measurement. We studied 26 women with postmenopausal osteoporosis (bone mineral density [BMD] T score < -2.5), who were randomized in a 2:1 ratio to receive alendronate (10 mg/day) and calcium carbonate (500 mg/day) or calcium carbonate alone for 6 months. We measured serum markers of bone formation (osteocalcin [OC], bone isoform of alkaline phosphatase [BAP], and collagen type I C-terminal propeptide [CICP]) and urinary markers of bone resorption (cross-linked N-telopeptide [NTx], free deoxypyridinoline [iFDpd], and free pyridinolines). All subjects had two measurements 1 week apart at baseline to calculate the short-term variability. Biochemical measurements were then made at 4, 8, 12, 24, and 25 weeks. Measurements of bone mass were made by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and proximal femur twice at baseline and then at 24 and 25 weeks. The mean difference in change in BMD and markers between both groups at the end of the study that were significant were (short-term variability in brackets): DXA total hip 4.3% (2.5%), NTX 49% (10%), iFDpd 22% (12%), OC 28% (13%), BAP 31% (13%), and CICP 31% (11%). Five of the six markers showed significant responses to alendronate therapy, but they differed in the relationship between size of response and variability. These biochemical markers performed better than DXA for monitoring alendronate therapy over 6 months.     

Uncemented acetabular components with bulk femoral head autograft for acetabular reconstruction in developmental dysplasia of the hip: results at five to twelve years.

BACKGROUND: Anterolateral acetabular bone deficiency is one of the technical problems associated with total hip arthroplasty in patients with developmental hip dysplasia. The purpose of this study was to evaluate the results of one method of acetabular reconstruction for hip dysplasia-placement of an uncemented socket in conjunction with a bulk femoral head autograft. METHODS: Forty-four hips in thirty-five patients (twenty-nine female and six male; average age, thirty-nine years) with developmental hip dysplasia were treated with primary total hip arthroplasty with use of an uncemented porous-coated titanium cup fixed with screws and an autogenous bulk femoral head graft. The patients were followed clinically in a prospective fashion for five to 12.3 years (mean, 7.5 years), and radiographs were analyzed retrospectively. RESULTS: Four acetabular components were revised: two, because of severe polyethylene wear and osteolysis; one, because of aseptic loosening; and one, because of fracture of the acetabular shell. The mean Harris hip score for the unrevised hips improved from 51 points preoperatively to 91 points postoperatively. No unrevised socket had definite radiographic evidence of loosening. Forty-three of the forty-four hips had no radiographic evidence of resorption of the graft or had radiographic evidence of resorption limited to the nonstressed area of the graft lateral to the edge of the cup. CONCLUSIONS: This method of reconstruction provided reliable acetabular fixation and appeared to restore acetabular bone stock in patients with developmental hip dysplasia. We use this technique for patients with moderate anterolateral acetabular bone deficiency requiring total hip arthroplasty.     

Cemented revision total hip arthroplasty with impaction bone grafting in Gaucher's disease

Total hip arthroplasty in Gaucher's disease has been associated with high rates of loosening after all types of arthroplasty. We present a patient with type 1 Gaucher's disease who underwent revision cemented total hip arthroplasty for aseptic loosening after 12 months of enzyme replacement therapy. Major osteolysis was managed by impaction morcellized bone grafting. An excellent clinical and radiographic result was obtained at 5-year follow-up. Enzyme replacement therapy combined with modern revision techniques may offer improved outcomes for patients with Gaucher's disease.     

Bone mineral density and biochemical markers of bone turnover in aseptic loosening after total hip arthroplasty.

The aims of this study were to determine whether subjects with aseptic loosening after total hip arthroplasty (THA) have regional differences in periprosthetic bone mineral density (BMD) and systemic biochemical markers of bone turnover compared to subjects with successful implants.Proximal femoral and pelvic BMD were measured by dual energy X-ray absorptiometry and bone turnover markers were assayed in 49 subjects 12.6+/-4.3 (mean+/-SD) years after cemented THA. Femoral BMD was lower in Gruen zones 2, 5, 6, and 7 in subjects with a loose femoral implant (n=17) compared to those (n=32) with fixed femoral implants (P<0.05 all comparisons). This BMD difference was greatest (-31%, P=0.02) in the proximal and medial region of the femur. Subjects with femoral loosening had higher levels of the bone resorption marker N-telopeptides of type-I collagen (P=0.02) than those with a fixed femoral implant. No differences in pelvic BMD or bone turnover markers were found between subjects with loose (n=18) versus fixed (n=31) pelvic implants.This study suggests that failure of femoral components after cemented THA is associated with region-specific decreases in BMD and an increase in urinary excretion of N-telopeptide cross-links of type-I collagen. These surrogate outcome markers may be of value in monitoring response to antiresorptive therapies used to treat periprosthetic osteolysis, although the diagnosis of aseptic loosening remains clinical and radiological.     

Biochemical markers can predict the response in bone mass during alendronate treatment in early postmenopausal women. Alendronate Osteoporosis Prevention Study Group

Data from the Danish cohort (n = 67) of a multicenter trial of oral alendronate in the prevention of postmenopausal osteoporosis were used to evaluate the capacity of the biochemical markers to predict changes in bone mineral density (BMD). A panel of markers were measured: serum N-terminal midfragment osteocalcin (N-MID OC); serum total osteocalcin (total OC); bone-specific alkaline phosphatase (BSAP); serum and urine C-telopeptides of type I collagen (sCL and uCL); urine N-telopeptide crosslinks of type I collagen (NTX); and deoxypyridinoline (dPyr). The correlation between change from baseline at months 3-12 in total OC, N-MID OC, sCL, uCL, and NTX and 2 year response in spine BMD ranged from r = -0.45 to r = -0.78 (p < 0.001), and from r = -0.38 to r = 0.10 (n.s. to p < 0.002) for BSAP and dPyr. Sensitivity and specificity were used to assess the accuracy of change from baseline at month 6 in the biochemical markers for predicting prevention of bone loss in the spine over 2 years. The cutpoints used were a 30% (N-MID OC) or 50% (all other markers) decrease from baseline. Sensitivity levels were 82% (N-MID OC), 98% (total OC), 78% (sCL and NTX), and 89% (uCL). Specificities were 91% (N-MID OC), 59% (total OC), 100% (sCL), 71% (uCL), and 84% (NTX). Positive predictive values were 95% (N-MID OC), 82% (total OC), 100% (sCL), 87% (uCL), and 90% (NTX). In comparison, the predictive capacities of change from baseline at year 2 in hip BMD in predicting prevention of bone loss at the spine were similar: sensitivity, 82%; specificity, 55%; and positive predictive value, 79%. In conclusion, short-term changes in biochemical markers were valid predictors of long-term changes in BMD. Short-term changes in the sensitive biochemical markers revealed a predictive capacity similar to bone densitometry at the hip measured over 2 years. The sensitive biochemical markers offered a fast and valid alternative to bone densitometry for monitoring of alendronate treatment.     

Bone-membrane interface in aseptic loosening of total joint arthroplasties

In 19 patients who underwent revision arthroplasty for aseptic loosening of total joint arthroplasty, specimens were taken at the time of operation to include the bone-membrane interface. In 16 (84%) of the specimens, sufficient visualization of the interface was possible to allow histologic interpretation. In 13 of these cases, there was prominent evidence of classic bone remodeling with osteoclastmediated resorption and active new bone formation. These results suggest that the osteolysis in aseptic loosening is mediated through osteoclastic bone resorption and that the bone found in such areas is extremely active. The findings help to explain the efficacy of impacted morselized bone-graft in the treatment of bone lysis in aseptic loosening.     

Ureaplasma urealyticum Infection in Total Hip Arthroplasty Leading to Revision

We describe an infection with Ureaplasma urealyticum causing rapid loosening of a cemented total hip arthroplasty. When reviewing the literature we found that no such case has been reported previously. Taking intraoperative cultures for U urealyticum during revision surgery is not a standard procedure. In cases with rapid, presumed aseptic, loosening of a total hip arthroplasty, an infection with U urealyticum should be considered.     

人工髋关节置换术后假体无菌性松动的临床及影像学评估

人工髋关节置换术(THA)后假体无菌性松动问题始终是临床上存在并需要解决的问题。通过临床及放射学检查，观察分析假体松动的表现与过程，对于人工髋关节置换术后假体松动的及时临床处理及预防均有指导意义。本对人工髋关节置换术后假体无菌性松动的临床及影像学评估方法进行了回顾和分析，指出临床及各影像学评估方法的意义，提出正确的评估原则。     

The Role of the Pathologist in Diagnosing Periprosthetic Infection

Most patients who undergo total joint arthroplasty experience dramatic relief of pain and improved ambulation for many years, but some eventually develop pain, often accompanied by radiographic evidence of bone resorption around their implants. The most frequent cause of device failure is osteolysis, but infection is another important cause of pain and arthroplasty failure. The distinction between infection and aseptic loosening is important because the 2 conditions are treated very differently. The purpose of this article is to summarize the role of the anatomic and clinical pathologist in helping distinguish aseptic loosening from infection.     

Failed Christiansen total hip arthroplasty. A radiographic and histologic study

Twenty-two consecutive cases of the Christiansen total hip arthroplasty revised because of aseptic loosening were analyzed with regard to radiographic changes and operative and histopathologic findings. This prosthesis was designed with a socket and a trunnion sleeve made of polyoxymethylene or Delrin. In 18 cases there was isolated socket loosening, in all cases there was obvious bone resorption beneath the collar of the stem, and in 20 cases the socket had migrated. The radiographic socket wear rate averaged 0.4 mm/year. In 18 cases a significant amount of debris material was found in the joint cavity. Light microscopy revealed a severe foreign body reaction with numerous plastic particles, most often engulfed by macrophages. Taken together, these findings indicate that socket wear leading to a foreign body reaction with bone resorption is the main cause of the poor results noted with this particular total hip prosthesis.     

Diurnal Variation of Bone Mineral Turnover in Elderly Men and Women

The diurnal variation of markers of bone mineral metabolism have been documented in pre- and early postmenopausal women. Such rhythms have clinical implications for timing of sample collection and assessment of therapeutic intervention. To examine the diurnal variation of bone turnover in the elderly, we examined markers of bone formation [serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP)]; a marker of bone resorption (urinary N-telopeptide cross-linked collagen type 1 [NTX]); and serum calcium and parathyroid hormone (PTH) over 24 hours. Subjects were healthy community-dwelling elderly who were on no medications known to significantly alter bone mineral metabolism. Subjects included 14 women [74 ± 6 years (mean ± SD)] and 14 men (80 ± 5 years). Over the 24-hour sampling period, mean serum OC, B-ALP, and calcium values were similar in elderly men and women. However, mean serum PTH was significantly higher in elderly men compared with women (P < 0.05). The magnitude of the diurnal variation of urinary NTX was significantly higher in women compared with men (P < 0.05). There was a significant diurnal variation for serum OC, B-ALP, calcium, PTH, and urinary NTX in both elderly men and women. The magnitude of the diurnal variation was approximately 10–20% of mean value for OC and B-ALP, 30% for PTH, and up to 40% for urinary NTX. We conclude that there is significant diurnal variation in the markers of bone mineral metabolism for elderly men and women. The peak value, which on average would be 20% higher than the mean value for urinary NTX, highlights the importance of the timing of sample collection for appropriate interpretation of therapeutic response. In addition, gender-related differences, including relatively higher levels of serum PTH and lower levels of urinary NTX in elderly men, may help explain differences in rates of bone loss in this age group. Received: 21 June 1996 / Accepted: 18 October 1996     

Effect of risedronate on bone metabolism after total hip arthroplasty: a prospective randomised study

Aseptic loosening due to bone remodeling and osteolysis is the main reason for revision hip arthroplasty. At present, there is no established prophylaxis for this complication. On the other hand, it has been demonstrated that bisphosphonates prevent bone loss around total hip arthroplasties (THA). The aim of this study was to assess the efficacy of oral bisphosphonate risedronate for the prevention of deleterious changes in bone metabolism after hip replacement. Twenty-four patients who underwent THA were randomised to two treatment arms: 35 mg risedronate once weekly for 6 months (12 patients) and no treatment for controls (12 patients). Markers of bone turnover bone specific alkaline phosphatase, serum osteocalcin and urinary deoxypiridinoline were evaluated at baseline, third and sixth postoperative month. Dual energy X-ray absorptiometry of the nonsurgical hip was performed preoperatively and at 6 months postoperatively. There were no significant differences in clinical or radiographic findings between the two groups at either 3 or 6 months. In the two groups, all biochemical marker responses at the third postoperative month were suppressed compared with baseline. Values of bone resorption marker urinary deoxypiridinoline increased significantly at six months in the control group. For the 10 risedronate patients with bone densitometry bone mineral density reached 1.01% increase at 6 months. Administration of oral risedronate led to a significant reduction in bone metabolism at 6 months after hip replacement. This therapeutic strategy may improve the results and longevity of total hip arthroplasty. The beneficial effect of risedronate should be confirmed in further studies including larger number of patients and longer follow-up. The action of risedronate could prevent aseptic loosening of hip arthroplasty by preserving periprosthetic bone stock.     

Low Revision Rates at More Than 10 Years for Dual-Mobility Cups Cemented Into Cages in Complex Revision Total Hip Arthroplasty

BackgroundInstability and aseptic loosening are the two main complications after revision total hip arthroplasty (rTHA). Dual-mobility (DM) cups were shown to counteract implant instability during rTHA. To our knowledge, no study evaluated the 10-year outcomes of rTHA using DM cups, cemented into a metal reinforcement ring, in cases of severe acetabular bone loss. We hypothesized that using a DM cup cemented into a metal ring is a reliable technique for rTHA at 10 years, with few revisions for acetabular loosening and/or instability.MethodsThis is a retrospective study of 77 rTHA cases with severe acetabular bone loss (Paprosky ≥ 2C) treated exclusively with a DM cup (NOVAE STICK; Serf, Décines-Charpieu, France) cemented into a cage (Kerboull cross, Burch-Schneider, or ARM rings). Clinical scores and radiological assessments were performed preoperatively and at the last follow-up. The main endpoints were revision surgery for aseptic loosening or recurring dislocation.ResultsWith a mean follow-up of 10.7 years [2.1-16.2], 3 patients were reoperated because of aseptic acetabular loosening (3.9%) at 9.6 years [7-12]. Seven patients (9.45%) dislocated their hip implant, only 1 suffered from chronic instability (1.3%). Cup survivorship was 96.1% at 10 years. No sign of progressive radiolucent lines were found and bone graft integration was satisfactory for 91% of the patients.ConclusionThe use of a DM cup cemented into a metal ring during rTHA with complex acetabular bone loss was associated with low revision rates for either acetabular loosening or chronic instability at 10 years.     

Circaannual rhythms and interactions of vitamin D metabolites, parathyroid hormone, and biochemical markers of skeletal homeostasis: a prospective study.

Recent studies suggest a circannual pattern of bone turnover. To further investigate the underlying mechanisms, 41 healthy subjects (25-80 years old) living in a southwestern German city were studied prospectively over a period of 18 months. Participants were examined every 4 weeks, and blood and urine samples were obtained on each visit. The following parameters were measured: serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and parathyroid hormone (PTH), as regulators, and serum total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), urinary total pyridinoline (PYD), deoxypyridinoline (DPD), and the aminoterminal telopeptide of collagen type I (NTX), as biochemical markers of bone turnover. The presence of significant circannual rhythms for the various markers was tested using the Pharmfit method. In the total group, 25(OH)D3, 1,25(OH)2D3, and PTH as well as BAP, PYD, DPD, and NTX showed a significant seasonal variation. 25(OH)D3 revealed the highest amplitude (38.0%) with an acrophase in August. Levels of the biochemical markers and of PTH were highest in winter with amplitudes of up to 17.7% (DPD). Results were most pronounced in premenopausal women, in subjects <50 years of age, and in subjects who did show a significant individual rhythm in 25(OH)D3 levels. No differences were found regarding other anthropometric or life style factors. Correlation analyses revealed strongest associations between the amplitudes of a vitamin D metabolite and a biochemical marker in premenopausal women. We conclude that specific markers of bone turnover show significant circannual rhythms. These changes are related directly to variations in the hormonal regulation of skeletal homeostasis. In postmenopausal women and in men, other effects may superimpose the circannual variation of biomarkers of bone turnover.     

Survival analysis of cementless grit-blasted titanium total hip arthroplasties

Although about 200000 cementless Zweymüller-Alloclassic total hip arthroplasties (THAs) were carried out worldwide in the last decade, the survival analysis of these prostheses was not available in the 2000 report of the Swedish national hip arthroplasty registry. We report a prospective survivorship analysis of 200 consecutive grit-blasted cementless Alloclassic primary THAs carried out since 1988. Using surgical, clinical and radiological endpoints for the stem and the threaded cup the ten-year survivorship was 91.5% for reoperation for any cause, 96.4% for hip pain (Merle d'Aubigné score < 5 points, clinical failure), 99.4% for definite aseptic loosening (radiological failure) and 99.3% for revision for aseptic loosening. Using the Swedish registry criteria of primary osteoarthritis and revision for aseptic loosening as the endpoint, the survival rate of 99.1% at ten years for the subgroup of 157 Alloclassic THAs in osteoarthritis compares favourably with that of the best modern cemented hip replacements reported in the Swedish arthroplasty registry.