Evaluation of bone metabolism in patients after total hip replacement based on bone turnover markers]

Serum bone markers: N-mid osteocalcin (OCN-Mid) and Cross-Laps were evaluated in 51 patients (15 men and 36 women), age 50-81y. (mean 69) with OA undergoing elective cemented THR. Samples were collected at the day before operation and 3 days, 1, 2, 6 weeks, 3, 6, 12 months after the operation and markers measured by direct chemoluminescency using Modular E-170. Lowest values of both markers were noted at the 3-rd day after operation. Cross-Laps levels rose rapidly reaching highest levels 2 weeks after operation and still were significantly (alpha = 0,05) elevated after 6 weeks. The highest but not statistically significant levels of OCN-Mid were noted after 6 months. After 12 months both markers returned to preoperative values. OCN-Mid/Cross-Laps ratio were lowest after 2 weeks (maximal resorption), then rose over the preoperative value after 3 months, being still significantly elevated after 12 months, indicating that bone formation still occurred. No significant differences were found according to sex, radiolucencies around the endoprosthesis (14 patients) and periarticular ossification (9 patients). Serum bone markers can show the process of bone healing around endoprosthesis, but because of different basic levels of bone metabolism, evaluation of this process can be achieved only with comparison to preoperative values.     

Increased urinary crosslink levels in aseptic loosening of total hip arthroplasty

The diagnosis of aseptic loosening in total hip arthroplasty is predominantly based on clinical and radiographic evaluation. Loosening is usually associated with increased bone resorption at the interface. In this study we wanted to evaluate the diagnostic value of bone markers in aseptic loosening. We compared 50 patients with proven component loosening during surgery with 50 age-, sex-, and implant-matched patients without clinical or radiological signs of loosening. We measured serum markers of bone formation (bone-specific alkaline phosphatase, osteocalcin [OC], procollagen type I propeptides) and bone resorption (collagen n-telopeptide [NTX], deoxypyridinoline [DPYD], pyridinoline [PYD]). We found significantly increased levels of NTX, DPYD, PYD, and OC in the loosening group. The other markers showed no significant difference between both groups. We conclude that determination of urinary crosslinks may offer a new and valuable diagnostic method in the detection of aseptic loosening in total hip arthroplasty.     

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.     

Tartrate-resistant acid phosphatase 5b (TRAP 5b) as a marker of osteoclast activity in the early phase after cementless total hip replacement

Background After total hip replacement, increased bone metabolism is seen. A local periprosthetic osteopenia can be measured by dual-energy X-ray absorptiometry (DXA), but it is still unkown whether biochemical markers can be used to monitor the local remodeling at an earlier stage.

Patients and methods In this prospective study we compared the biochemical markers tartrate-resistant acid phosphatase 5b (TRAP 5b), bone ALP, osteocalcin and CrossLaps with periprosthetic DXA in 17 consecutive patients after uncemented total hip replacement.

Results We found a highly significant early increase in TRAP 5b after 2 weeks and 6 weeks, which was followed by a densitometrically detectable decrease in bone mineral density after 26 weeks, especially in periprosthetic section Gruen zone 7. Bone ALP and osteocalcin levels as markers of osteoblast activity, and also Cross-Laps as a further marker of osteoclast activity, did not appear to allow any significant prediction of local bone remodeling.

Discussion Our findings show that TRAP 5b is a sensitive parameter for monitoring of osteoclast activity after cementless total hip replacement, and may predict local osteopenia.     

Decreased tibial bone strength in postmenopausal women with aseptic loosening of cemented femoral implants measured by peripheral quantitative computed tomography (pQCT)

Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The aim of the present study was to investigate the effect of aseptic loosening on volumetric bone mineral density (vBMD) and bone geometry in the operated leg, in postmenopausal women with a loosened cemented femoral implant using peripheral quantitative computed tomography (pQCT). We matched 12 postmenopausal women with aseptic loosening of cemented femoral implant, with 12 women without aseptic loosening (control group) according to age, BMI, and years from operation. All patients underwent pQCT of both tibias, DXA of the lumbar spine, and determination of biochemical markers of bone turnover. pQCT values in the control group as well as the nonoperated legs between groups had no significant difference. In the aseptic loosening group, there was significant reduction of cortical vBMD (cort vBMD) at 14% and 38% sites (cortical site), cortical thickness at 38% site, and of polar stress strength index (SSIp) at 14% site (transition zone) in the operated compared with the nonoperated leg. Similarly, there was significant reduction of cort vBMD at 14% and 38% sites and total vBMD and trabecular vBMD (trab vBMD) at the 14% site in the operated legs between the two groups. The aseptic loosening group had increased osteocalcin and serum collagen cross-linked N- and C-telopeptides (sNTX and sCTX) levels compared with controls. Aseptic loosening is associated with significant decrease of cortical and trabecular vBMD, and impairment of bone geometry and strength only in the operated leg. Increased bone turnover probably represents a local phenomenon, and is not associated with systemic skeletal 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.     

Outcome of uncemented hip arthroplasty components in patients with Paget's disease

The outcome of uncemented hip arthroplasty in patients with Paget's disease is unknown. The clinical and radiographic records of patients with Paget's disease affecting the hip who had total hip arthroplasty using uncemented components against pagetic bone were reviewed. There were 18 patients (19 hips) with an average age of 71.3 years (range, 54-85 years). Followup averaged 7 years (range, 2-15 years). Surgery often was reported to be demanding technically because of hard sclerotic bone and excessive bleeding in some patients. Estimated blood loss averaged 996 mL (range, 200-2500 mL). Harris hip scores improved significantly. There was clinical and radiographic evidence of bone ingrowth in all patients. Six of 19 hips had heterotopic bone. One hip had severe Brooker Grade IV heterotopic ossification and the patient required excision of the ossification at 5 years. One hip was unstable (subluxating) at the latest followup. There was no revision for component loosening and no recognized cases of clinical or radiographic loosening of any uncemented implants. Results of total hip arthroplasty using uncemented components in patients with Paget's disease are excellent overall, with an extremely low risk of component loosening during the first decade after implantation. These patients may be at higher risk for heterotopic bone formation and increased perioperative blood loss because of hypervascularity of the bone.     

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.     

Assessment of Five Interleukins in Human Synovial Fluid as Possible Markers for Aseptic Loosening of Hip Arthroplasty

One of the most important factors that seems to be involved in total hip replacement is periprosthetic osteolysis. As it is well documented that several interleukins (ILs) are triggered in periprosthetic osteolysis, this article investigates the role of five ILs in primary and replacement total hip arthroplasty, understanding if one of them can also predict hip implant loosening, secondary surgery, and prosthesis breakage. The levels of IL-1α, 1β, 6, 8, and 10 in synovial fluid were examined, using a high sensitivity enzyme-linked immunosorbent assay (ELISA) test kit (Pierce Biotechnology, Inc., Rockford, IL, USA) to determine whether these cytokines could be used as markers of enhanced periprosthetic osteolysis, leading to aseptic loosening of total/partial hip arthroplasty or revision surgery. Synovial fluid was harvested from 23 patients undergoing primary total hip arthroplasty and 35 patients undergoing total/partial hip revision due to aseptic loosening. In the revision group, four cases had suffered a prosthesis fracture and five were second revisions. ILs 6 and 8 were significantly higher in the revisions (305 and 817 pg/mL) compared with the primary arthroplasties (151 and 151 pg/mL), including cases with prosthesis fracture and those requiring a second revision. IL-10 levels were lower (not significantly) in second revision samples compared with those of revision samples. IL-1β levels were significantly higher in prosthesis fracture samples compared with those of all the other revision samples. No statistically significant differences in IL levels were found between osteoarthritis samples and those of other diseases. These results are a step forward to elucidating the complex network of events that are involved in loosening of hip implants.     

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.     

Cellular mediators secreted by interfacial membranes obtained at revision total hip arthroplasty

The interfacial membrane between implant and host—bone in aseptically loose total hip arthroplasties has a potential role in the etiology of local bone resorption and loosening of the prosthetic component. Inflammatory/potential “bone-resorbing” agents (cytokines/mediators) released by the cells of the interfacial membranes of loosened uncemented and cemented total hip arthroplasties were measured. Synovial tissues from patients with acute femoral neck fractures, patients with osteoarthritis, and cadavers without joint disorders were used as control subjects. Control synovial tissue from osteoarthritic patients secreted the highest levels of prostaglandin E₂, interleukin-8, and tumor necrosis factor alpha. Interleukin-1α was the only cytokine whose levels were elevated as much as 4-fold around uncemented implants compared with cemented implants, and up to 16-fold compared with control synovial tissue. An apparent inverse relation between interleukin-1α and interleukin-6 interfacial membranes of total hip arthroplasties compared with control synovial tissues suggests a complex cellular mechanism through a cytokine/prostaglandin cascade; this may regulate the observed bone resorption in aseptic loosening.     

全髋关节翻修术中髋臼骨缺损的处理方法

目的探讨全髋关节翻修术中对于髋臼骨缺损重建的方法及其术后疗效。方法回顾性分析自2007-03—2011-12的75例（76髋）全髋关节翻修术,髋臼骨缺损根据Paprosky分型：Ⅰ型9髋,ⅡA型21髋,ⅡB型18髋,ⅡC型11髋,ⅢA型10髋,ⅢB型7髋。髋臼骨缺损采用不同方式修复,术后定期随访。采用髋关节功能Harris评分评估髋关节功能,根据X线片判断假体是否松动、植骨是否融合。结果 75例（76髋）均获得平均36（16~73）个月随访。术后12个月不同类型骨缺损患者髋关节功能Harris评分较术前明显提高,差异有统计学意义（P〈0.05）。术后症状和关节功能明显改善,未出现髋臼骨折、感染、下肢深静脉血栓形成、坐骨神经损伤等严重并发症。X线片可见移植骨与宿主骨质交界处有连续性骨小梁通过,假体未见松动迹象。结论髋臼假体无菌性松动及骨溶解是需要进行全髋关节翻修的主要原因,而髋臼骨缺损Paprosky分型法对髋臼翻修重建方法有指导意义,正确选择假体类型及合理选择植骨方式是全髋关节翻修术后取得满意疗效的保证。     

Bone turnover markers and cytokines in joint fluid: analyses in 10 patients with loose hip prosthesis and 39 with coxarthrosis

We analyzed bone turnover markers (osteocalcin, bone ALP, beta-crosslaps-CTX) and cytokines (IL-1, IL-8 and IL-10) in hip joint fluid in 10 patients before revision surgery and in 39 with idiopathic coxarthrosis. Patients with loose implants had lower concentrations of resorption marker than those with arthrosis (0.8 vs 1.3 ng/mL), but bone formation marker osteocalcin was reduced (4.2 vs 22.6 ng/mL). IL-8 and IL-10 levels were elevated in patients with implant failure (870 vs 340 pg/mL; 14.3 vs 4.0 pg/mL). We found a negative correlation between the bone resorption marker (CTX) and IL-10 in cases with prosthesis loosening and a positive correlation between IL-10 and time-to-revision. We conclude that enhanced local production of inflammatory cytokines leading to suppressed bone formation is a part of the loosening process. The expression of anti-inflammatory mediators is not sufficient to counteract the imbalance in bone turnover.     

Radiation therapy to prevent heterotopic ossification after cementless total hip arthroplasty

Clinical and roentgenographic observations on a postoperative low-dose radiation of 1000 cGy for prevention of heterotopic ossification in high-risk patients after 48 noncemented total hip arthroplasties demonstrated no overall statistical difference in the Harris hip scores between the treated group (92.2) and the control group (91.0). There was no difference in the incidence of radiolucent lines about the components, and there were no revisions for aseptic loosening in the treated group. The incidence of clinically significant (Brooker Grades III and IV) heterotopic bone formation was lower in the treated group (7%) than in the control group (32%). This difference in the incidence of heterotopic bone formation was statistically significant. Radiation therapy was effective in preventing postoperative heterotopic bone formation in biologically fixed total hip implants.     

Hydroxyapatite-coated total hip arthroplasty in osteoporotic patients

A prospective review was performed on 22 osteoporotic patients (rated from 1 to 3 on the Singh Index) with hydroxyapatite-coated total hip replacements. These results were compared with a control group (Singh Index 4 to 6) of 45 patients (48 hips) with respect to clinical and radiographic data. Surgery was performed over a six-year period (1991 to 1996) and the time to follow-up evaluation averaged 5 years (range: 2 to 7 years). All patients, in both groups, were over 65 years old with an average age of 71 and 73 years, respectively. The pre-operative diagnoses and Harris hip scores were also similar for both groups. Clinical evaluation was based on the Harris Hip score and radiographic evaluations using Engh's criteria. There was no significant difference between the final average Harris hip score in the osteoporotic bone group, which was 87 points, and that for the control group, which was 91 points (p > 0.05). Radiographic evaluation demonstrated confirmed bone ingrowth in most patients in each group; one patient in each group had suspected bone ingrowth. No stems were revised for aseptic loosening and no endosteal lysis was found. Progressive bone formation was seen around the femoral stem proximally. The acetabular components demonstrated no sign of mechanical loosening or osteolysis. Bone formation was found in most patients in zone I, and in a few patients also in zone III. On the basis of the results of this study, it is believed that osteoporotic bone as a factor by itself should not compromise the early results of hydroxyapatite total hip arthroplasty and should provide good results in the long term.     

珊瑚型人工髋关节置换术的临床随访及松动原因的分析

自１９８３年至今应用珊瑚型人工髋关节置换术共５４例６０髋。其中人工全髋关节置换术３４例４０髋，人工股骨头置换术２０例２０髋。在５４例６０髋珊瑚型人工髋关节置换术中，有３７髋随访６个月～１３年，平均随访时间约７年，疗效满意率为８５．１％，其中假体松动４例占１４．８％，髋臼松动２例７．４％。假体松动原因是假体与股骨负重界面之间没有达到稳定接触，假体与髓腔形状不相匹配，修整髓腔松质骨时，髓腔扩大器应比假体小一号，避免假体与界面存留缝隙。对于髋臼发育不良的患者应避免髋关节旋转中心向外侧移位，应向内上方加深髋臼以减少水平移位距离，其次髋臼植骨加盖勿在负重区。     

Preparation of the acetabulum to correct severe acetabular deficiency for total hip replacement--with special reference to stress distribution of the periacetabular region after operation

The author analysed the radiological results of eighty-three total hip replacements in the patients with severely defective acetabulum secondary to congenital hip dysplasias or failed total hip replacements, after an average follow-up period of three years, paying particular attention to socket loosening. The patients with congenital hip dysplasias were divided into the following four groups: Group 1: The sockets were placed above the level of true acetabulum. Group 2: The sockets were placed in the true acetabulum with the cement used as a filler superolaterally. Group 3: The sockets were placed in the true acetabulum with bone grafts. Group 4: Eccentric sockets were placed in the true acetabulum. The incidence of radiological loosening of the socket was 50% in the group 1, 13% in the group 2, 6% in the group 3 and 75% in the group 4. The patients who underwent revision for socket loosening were also divided into two groups, the one whose acetabula were reconstructed with bone grafts and the other without bone graft. The incidence of radiological loosening of the socket was 28% in the group with bone grafts and 72% in the group without bone graft. The major factor that may have been responsible for socket loosening in these cases was considered to be poor mechanical condition around the socket due to bone deficiency. Two-dimensional finite element analysis was performed to establish the stresses in the periacetabular region after total hip replacement for acetabular deficiency. Model variations include, the conventional plastic socket of 44 mm outside, 28 mm inside diameter placed in false acetabulum or in high level, (2) in true acetabulum using bone cement as a filler, (3) in true acetabulum with bone graft and (4) eccentric socket placed in true acetabulum without bone graft. The ratio of von Mises stress to yield stress of each element were calculated. The results demonstrated that in the periacetabular region, the area superomedial to the socket was at high risk in each model. The area in periacetabular bone where the ratio of von Mises stress to yield stress was more than 20% was almost the same in model (1), (2), (4) and about a half of them in model (3). In conclusion, the most effective method to prevent the socket loosening after total hip replacement in the patient with deficient acetabulum was considered to reconstruct the new spherical acetabulum at anatomical position with bone graft.     

Systemic cross-linked N-terminal telopeptide and procollagen I C-terminal extension peptide as markers of bone turnover after total hip arthroplasty

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV).The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects.A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.     

Knochentransplantation mit Hüfttotalendoprothese bei diffuser pigmentierter villonodulärer Synovitis

Pigmented villonodular synovitis (PVNS) is a rare benign but aggressive disease of the synovium. If the hip is involved early destruction of the joint is common due to the tight structure of the capsule and arthroplasty is unavoidable in these cases. We implanted a cemented total hip replacement in a 17-year-old female patient who had histologically confirmed PVNS. Because of massive bony destruction in the acetabulum a reconstruction with homologous bone (two femoral heads) from the bone bank was necessary. After 5 years the bone transplant had become integrated, there were no signs of recurrence and the patient was pain-free with a normal joint function. There were no signs of loosening.