Primary hip arthroplasty for the treatment of alkaptonuric hip arthritis: 3- to 24-year follow-ups RESEARCH Open Access Primary hip arthroplasty for the treatment of alkaptonuric hip arthritis: 3- to 24-year follow-ups Javahir A. Pachore1, Vikram Indrajit Shah1,2, Sachin Upadhyay3,4* , Kalpesh Shah5, Ashish Sheth5 and Amish Kshatriya5 Abstract Background: The objective of this study is to share our experience in total hip replacement for the treatment of ochronotic hip arthritis, in particular to report how to establish the diagnosis and some tips to limit complications. Method: A cohort comprised of 10 patients (12 hips) with alkaptonuric hip arthritis. There were six men and four women with the mean age of 62.80 ± 7.57 years. All patients had a stiff spine, grossly restricted movements of hip joints, and severely limited daily routine activities. Total hip replacement was performed in all patients. The patients were evaluated at 6, 12, and 24 months after surgery, as well as every 4 years thereafter. Harris hip score was used to assess the functional outcome. The level of significance was set at p < 0.05. Results: The mean follow-up lasted 16.70 ± 6.82 years (3 to 24 years). At the final available follow-up, nine patients returned to work, ambulate without an orthosis, and achieve complete pain relief. Harris hip score was improved from poor to excellent. One patient died 16 years after surgery due to breast cancer. No complication relating to prosthetic failures was detected. Conclusion: Total hip replacement gives long-term satisfactory results in patients with alkaptonuric hip arthritis, resulting in comparable function of the hips in patients who undergo primary osteoarthrosis. Keywords: Total hip replacement, Alkaptonuric arthritis, Ochronosis, Harris hip score Background First described by Virchow in 1866, ochronosis is the con- nective tissue manifestation of alkaptonuria, an autosomal recessive mutation of the HGO gene on chromosome 3q, caused by deficiency of homogentisate 1, 2 dioxygenase activity [1]. Homogentisic acid oxidase is responsible for turnover of homogentisic acid (HGA) during the course of phenylalanine and tyrosine catabolism [2]. HGA accumu- lates and is polymerized into a blue-black pigment that is ultimately deposited in skin, bones, tendons, articular carti- lages, synovial membranes, lungs, valves, and kidneys [3]. The accumulation eventually causes severe degeneration of the spine and peripheral joints, which may clinically lead to common arthritic disorders [4]. Alkaptonuria is a rare metabolic disorder characterized by a triad of degenerative arthritis, ochronotic pigmentation, and homogentisic acid- uria, affecting one in 250,000 to 1 million people [5, 6]. Chromatographic, enzymatic or spectrophotometric deter- minations of HGA are confirmatory tests. Currently, there is no definitive cure for alkaptonuric ochronosis. Symptom- atic treatment of the complications of alkaptonuria is the only option, including pain management, physiotherapy, chiropractic care, and instruction regarding a home exer- cise program. A successful treatment for tendon ruptures caused by ochronosis is primary repair [6]. High dose of vitamin C decreases urinary benzoquinone acetic acid, but has no effect on HGA excretion and, moreover, no cred- ible studies have shown that treatment with vitamin C is clinically effective. Nitisinone, a potent inhibitor of 4- hydroxyphenylpyruvate dioxygenase, dramatically reduces © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. * Correspondence: drsachinupadhyay@gmail.com Institution(s) at which the work was performed: Shalby Hospitals in Ahmedabad, Gujarat 3Department of Orthopaedics, NSCB Medical College, Jabalpur, MP, India 4Department of Trauma, Joint Replacement and Minimal Invasive Surgery, Shalby Hospitals Jabalpur, Jabalpur, Madhya Pradesh, India Full list of author information is available at the end of the article ArthroplastyPachore et al. Arthroplasty (2019) 1:8 https://doi.org/10.1186/s42836-019-0010-8 http://crossmark.crossref.org/dialog/?doi=10.1186/s42836-019-0010-8&domain=pdf http://orcid.org/0000-0002-2640-0147 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/publicdomain/zero/1.0/ mailto:drsachinupadhyay@gmail.com production and urinary excretion of homogentisic acid [7], however, the effectiveness of Nitisinone in treating ochronosis remains unknown. Patients with alkaptonuria are usually asymptomatic, and the ochronotic arthropathy appears after the fourth decade [8]. Total replacement of hip, knee, elbow, and shoulder can alleviate pain and in- crease patient’s daily activities [2]. There is a paucity of studies concerning total hip replacement in the present patient population with adequate follow-up statistics. The primary objective of the present study is to share our experience in total hip replacement (THR) for ochro- notic hip arthritis, in particular to report on establishment of diagnosis and tips to decrease the complications. Patients and methods The study was approved by the Institutional Ethics Committee of the hospital. Informed consent was ob- tained from each patient. A case series of 10 patients (12 hips) with alkaptonuric hip arthritis who presented to our institute were reported. There were six men and four women with the mean age of 62.80 ± 7.57 years (range, 53–80 years). Demographic vari- ables, presentation, comorbidities, and preoperative diagno- ses were recorded and analyzed (Table 1). All patients had pain in groin region for the past 4 months to several years. None of the patients was under specific treatments. Clin- ical, imaging, and laboratory assessments were performed in all patients. Of the 10 patients, seven patients had a fam- ily history of alkaptonuria, and eight patients had cutaneous signs of ochronosis. Nine patients had a history of blackish discoloration of urine on exposure to air. Spine examin- ation revealed stiff spine with limited movements in all pa- tients. On local examination, hip movements were painful and severely restricted. All patients reported gross limita- tion of daily routine activities and needed assisted ambula- tion. A dried urine spot (DUS) [9] detects HGA in all patients. Other laboratory parameters were within the nor- mal ranges. The standard radiographs of hip showed severe joint degeneration and narrowing of the joint space with ir- regularity and flattening of the femoral head (Fig. 1a, b). A lateral spine radiograph revealed osteoporosis, flattened and intra-discal calcification, and variable degrees of fusion of the vertebral bodies (Fig. 2a, b). Pre-operatively, the mean Harris Hip Score was 35.00 ± 14.06. All patients were diag- nosed with ochronotic hip arthritis, and underwent primary hip arthroplasty. Eight patients underwent unilateral sur- gery and two had bilateral procedures. In bilateral cases, the priority was given to the side with more severely affected joint. Surgical technique All surgeries were performed by the same senior surgeon and the same arthroplasty team through the posterior approach with the patients in the lateral decubitus pos- ition. The incision was made over the center of the tro- chanteric region and then was adequately lengthened both cranially and caudally for a good exposure to avoid force- ful retraction. The subcutaneous fat was incised deep to the fascia lata. We found black discoloration over the ten- sor fascia lata, and calcification and hard tissue at the in- sertion of gluteus maximus tendon with blackish deposits (Fig. 3). We found deposition of black tissues with some degrees of fragility in the gluteus medius tendon. The fascia lata was incised and the gluteus maximus tendon was bluntly splited along the direction of fibers. The tro- chanteric bursa overlying the external rotators was incised. The sciatic nerve was carefully protected. The short exter- nal rotators were tagged with a suture for identification and subsequent repair. These rotators were detached at their insertions onto the greater trochanter and reflected posteriorly to expose the posterior joint capsule. The cap- sule was found to be more fibrotic and contracted with blackish discoloration. If the capsule was hard and contracted, we usually incised the capsule from 6 o’clock to 12 o’clock to ease dislocation of the femoral head. When the hip was dislocated, we found the femoral head was covered with typical black painted articular cartilage, but the subchondral bone was not affected (Fig. 4a). The tip of the trochanter was impregnated with thick black pigments. During the preparation of the femur, great care should be taken to avoid fracturing the tip of trochanter. Preparation of the acetabular bone was difficult due to the black deposition that looked like a layer of tissue (Fig. 4b). The bone was sclerotic, hard, and difficult to ream, so as to open subchondral bone (Fig. 4b). We conducted either pre-drilling or curettage of the cup and finally reamed it to get punctate bleeding. Furthermore, owing to the scler- otic rim cup, expansion of the acetabulum was probably difficult. Therefore, additional screws were used to secure the fixation. After trailing, the final cup position was achieved within the safe zone for both anteversion and in- clination. The femoral preparation was done in the rou- tine fashion, because the femoral canal was normal. After placement of the optimal stem and femoral head, THR was completed and hip joint was reduced. Closure was done in layers under negative suction drain. Postoperative managements The pigmented cartilaginous surface, bone, and soft tis- sues were sent for histomorphological evaluation. Our protocol was to remove the drain on the second postoper- ative day. The patient was discharged on the sixth postop- erative day, and then given a standard rehabilitation. Postoperative evaluation All patients returned for follow-ups at 6, 12, and 24 months, as well as every 4 years thereafter. Preoperatively Pachore et al. Arthroplasty (2019) 1:8 Page 2 of 9 T a b le 1 C h ar ac te ris ti cs o f p at ie n ts C as e A g e/ se x D u ra ti o n o f p ai n Si d e o f h ip C u ta n eo u s m an ife st at io n s U rin e d is co lo ra ti o n Fa m ily h is to ry Sp in e C o m o rb id it ie s Pr es en ta ti o n La st fo llo w u p 1 53 /M 3 ye ar s Le ft Pr es en t Ye s Ye s St iff w it h re st ric ti o n o f m o ve m en ts N il Bi la te ra l g ro in p ai n ;D is tu rb ed sl ee p ; n ee d ed as si st an ce in th e fo rm o f el b o w cr u tc h es to w al k; u n d er g o n e b ila te ra l to ta l kn ee re p la ce m en t 2 ye ar s b ac k Pa tie n t w as ad vi se d Ri g h t si d e u n ce m en te d to ta l h ip re p la ce m en t. 3. 7 ye ar s 2 55 /M 1 ye ar Ri g h t Pr es en t Ye s Ye s St iff w it h re st ric ti o n o f m o ve m en ts N il Ri g h t g ro in p ai n ;u n ab le to w al k fo r m o re th an 5m in s, sl ee p w as d is tu rb ed 16 .4 ye ar s 3 80 /F 4 m o n th s Bo th A b se n t Ye s N o St iff w it h re st ric ti o n o f m o ve m en ts H yp er te n si o n ,D ia b et es , Is ch em ic H ea rt d is ea se , Va lv u la r ca lc ifi ca ti o n , H yp o th yr o id is m Pa in in le ft si d e o f g ro in fo r p as t 4 m o n th s an d p ai n in b o th th e kn ee s; u n ab le to w al k d u e to p ai n . Ri g h t to ta l h ip re p la ce m en t w as d o n e ye ar s b ac k. 15 .7 ye ar s (R ig h t h ip ) 13 .7 ye ar s (le ft ) 4 65 /F 10 ye ar s Bo th Pr es en t Ye s N o St iff w it h re st ric ti o n o f m o ve m en ts H yp er te n si o n ,D ia b et es Pa in in b o th g ro in ,a lo n g w it h b ila te ra l kn ee p ai n an d b ac k p ai n fo r p as t 10 ye ar s; Pa ti en t w as b ed rid d en an d d is ab le d w it h p ai n 18 .5 (L ef t) 16 .7 (r ig h t) ye ar s (b ila te ra l h ip ) p at ie n t d ie d ~ 16 ye ar s af te r th e se co n d su rg er y 5 63 /F 6 m o n th s Le ft Pr es en t Ye s N o St iff w it h re st ric ti o n o f m o ve m en ts H yp er te n si o n ,D ia b et es , H ia tu s H er n ia ,U m b ili ca l h er n ia ,p ep ti c u lc er Pa in in th e le ft g ro in fo r th e p as t 6 m o n th s. Sh e al so h ad p ai n in b o th th e kn ee s an d sh o u ld er w it h lim it at io n o f m o ve m en ts . 22 .5 ye ar s 6 66 /F 10 m o n th s Le ft Pr es en t Ye s Ye s St iff w it h re st ric ti o n o f m o ve m en ts H yp er te n si o n ,D ia b et es ; O b es e Pa in in b o th th e g ro in fo r p as t 10 m o n th s. Le ft h ip w as m o re p ai n fu l th an th e rig h t si d e ca u si n g d iff ic u lt y in w al ki n g an d n ee d o f as si st an ce in th e fo rm o f w al ke r to w al k. Lo w Ba ck ac h e 19 .2 ye ar s 7 60 /M 1 ye ar s Ri g h t Pr es en t Ye s Ye s St iff w it h re st ric ti o n o f m o ve m en ts H yp er te n si o n ,D ia b et es Sp o n ta n eo u s an d in cr ea si n g p ai n in b o th h ip s, m o re se ve re o n th e rig h t. Lo w b ac ka ch e w it h d iff ic u lt y in w al ki n g 20 .2 ye ar s 8 64 /M 1. 5 ye ar s Ri g h t Pr es en t Ye s Ye s St iff w it h re st ric ti o n o f m o ve m en ts H yp er te n si o n ,D ia b et es Pr o g re ss iv e p ai n in rig h t h ip jo in t fo r th e la st 1. 5 ye ar s an d lo w b ac k ac h e fr o m th e la st 10 ye ar s. O rt h o si s as si st ed w al ki n g 10 .5 ye ar s 9 57 /M 2 ye ar s Ri g h t A b se n t N o Ye s St iff w it h re st ric ti o n o f m o ve m en ts N il Pa in in rig h t g ro in si n ce 2 ye ar s w ith m ar ke d re st ric ti o n o f m o ve m en ts . 24 .1 ye ar s 10 65 /M 10 m o n th s Le ft Pr es en t Ye s Ye s St iff w it h re st ric ti o n o f m o ve m en ts H yp er te n si o n Pa in w as d u ll ac h in g ,i n si d io u s in o n se t, co n ti n u o u s in n at u re m o re o n th e le ft si d e th an rig h t, in te rf er in g w it h h is d ay to d ay ac ti vi ti es 18 .9 ye ar s Pachore et al. Arthroplasty (2019) 1:8 Page 3 of 9 and at the final follow-up, functional outcome evaluation was performed using HHS. Standard anteroposterior and lateral femoral X-rays were obtained to study heterotopic ossification, radiolucent lines, position of stem and subsid- ence, the change in the cup inclination or cup migration, and loosening of implants. All parameters were expressed as mean ± standard deviation. The differences were ana- lyzed with student’s t test. A p < 0.05 was considered sta- tistically significant. Results In this series, the postoperative course was uneventful. No intraoperative complications other than increased blood loss were observed. Histopathological examination of periarticular tissues revealed that tissue pigmenta- tion was most markedly in the deeper layers, with areas of calcification and degeneration. The synovium was thickened, inflamed, and pigmented. HGA was detected using dried urine spots [9] in all patients. In all cases, Fig. 1 a & b Anteroposterior and lateral X-ray films of the pelvis, with both hip joints showing reduced join space with degenerative changes, irregularity, and flattening of femoral head Fig. 2 a & b Anteroposterior and lateral spine X-ray films revealed osteoporosis, flattened, and intra-discal calcification (doubling signs), and variable degrees of fusion of the vertebral bodies Pachore et al. Arthroplasty (2019) 1:8 Page 4 of 9 there was a macroscopic layer of black pigmented articu- lar cartilage, which was more severe in elderly patients. Histopathological, physical, biochemical, and radio- graphic evaluations confirmed the diagnosis of ochrono- tic arthropathy. One patient died 16 years after the second hip surgery due to breast cancer. Therefore, a total of 10 hips were followed-up finally. The mean fol- low-up time was 16.70 ± 6.82 years (range, 3 to 24 years). At 6-month follow-up, the mean HHS improved signifi- cantly, from 35.00 ± 14.06 preoperatively to 93.20 ± 1.75 (p < 0.05). Radiographs showed stable prostheses in situ without any evidence of subsidence (Fig. 6a, b, c, d, e, f, g and Fig. 7a, b, c, d). The latest follow-up showed that nine patients (10 hips) went back to work and ambulated without walking aids. All patients had complete pain re- lief. HHS was improved from poor to excellent. Al- though patients had complaints pertaining to low backache, none of the patient had major complications requiring a revision surgery. We did not found compli- cations related to prosthetic failures (Fig. 6a, b, c, d, e, f, g and Fig. 7a, b, c, d). Discussion Alkaptonuria is a rare autosomal recessive inborn meta- bolic disorder of tyrosine metabolism due to deficiency of homogentisic oxidase enzyme. Alkaptonuria is charac- terized by excretion of homogentisic acid in urine, and deposition of oxidized homogensitate pigments in the Fig. 3 Black discoloration over the tensor fascia lata, and calcification of the hard tissues with blackish deposit over the gluteus muscles Fig. 4 a A classical black painted articular cartilage of the femoral head; b A black painted articular cartilage of the acetabulum with sclerosis Pachore et al. Arthroplasty (2019) 1:8 Page 5 of 9 connective tissues and articular cartilages (ochronosis). The gene for this pathological condition is present at locus 3q21–23 [10]. In ochronosis, there is deposition of pigments from homogentisic acid in all types of connect- ive tissues, including cartilage, cardiovascular system, genitourinary system, sclera, skin, and ear cartilage [11, 12]. Urine discoloration is the first clinical manifestation of alkaptonuria, followed by color changes of the sclera and ears. Based on the detailed general examination, cu- taneous signs of ochronosis include color changes of the sclera and ears which can easily be observed (Fig. 5). 80 % of cases in our series had positive association. There is a paucity of available literature concerning the occur- rence of ochronosis arthropathy without ocular and cu- taneous signs. Kusakabe et al. [13] showed cervical arthropathy without ocular and dermatological findings. Retrospective inquiry for the family history of alkapto- nuria usually makes sense. In the present ten patients, seven had a positive family history. Patients will respond to the leading question about discoloration of urine. Ninety percent of the patients in our series had a history of blackish discoloration of urine on exposure to air. The tendons and ligaments may also be affected be- cause of their high collagen content. It causes inflamma- tory alterations resulting in rupture of the tissues [6]. Early diagnosis of ochronosis is valuable to avoid tendon ruptures. The preoperative cardiac clearance is impera- tive to rule out the risk of valvular calcification [12]. In our series, one patient who had a history of valvular cal- cification underwent aortic valve replacement and cor- onary artery bypass graft surgery. Alkaptonuric arthropathy has previously been shown to be a relatively benign disease. Our evidence showed that the patients with this disease were crippled and dis- abled with pain. Recent overall increase in life expect- ancy may account for the scenario. Although alkaptonuria affects both men and women with ochro- notic arthropathy, the trend is more severe and more frequent for men than for women. The result is also male preponderance (six men), which was compatible with our series [14, 15]. Patients with alkaptonuria are usually asymptomatic, and arthropathy appears after the third or fourth decade with a sudden onset of pain limiting daily routine activities [15, 16]. A late onsets is attributed to the gradual age-re- lated decline in the renal ability to excrete homogentisic acid, resulting in a diseased association with signs and symptoms of accumulation of homogentisic acid. In about 50% of patients, alkaptonuric cases develops arthropathy [17]. Low backache precedes joint diseases. In our cases, low backache with restricted mobility was on the fore- ground. In most of the cases, spinal examination showed the restricted movements of the spine. Back pain and stiff- ness in the thoraco-lumber junction and cervical region may be the initial symptom of ochronosis. The spinal stiff- ness is almost like ankylosing spondylitis but the age group is different. Pain is more severe in patients with an- kylosing spondylitis than in patients with ochronosis, which have an increased degeneration that may not pro- portionally increase severity of pain. There is a loss of cer- vical or lumbar lordosis. There may be kyphosis or localized scoliosis. In a few of such cases, root pain or sci- atica could be the presenting or only symptom in ochro- notic arthropathy. Spine radiograph shows intra-discal calcifications giving a “doubling” of the outline, which confirmed the diagnosis of ochronosis [18]. In patients with ankylosing spondylitis, there is extensive ossification of spinal ligaments with little calcification of the interver- tebral discs. Ochronotic arthropathy usually involves the large weight-bearing joints (knee and hip joints) rather than the small joints of the hand and foot [19–21]. In our series, the hip joints were severely affected. Movements of the hip joints were painful and were restricted due to the ar- thropathies. Similar to patients with primary osteoarthro- sis, concentric reduction of the joint space is frequently seen on X-rays. However, the radiological alterations may be much less apparent than the clinical manifestations. Intraoperatively, we noticed an increased blood loss, which may be the result of en bloc synovectomy of the hypertrophied synovium. The blood loss was more than what is usually observed in arthritis of other common causes. Although the hemoglobin and haematocrit levels were not decreased after surgery, we still advise to avoid total synovectomy without intraoperative bleeding control. Fig. 5 Cutaneous signs of ochronosis that include changes of the color of the sclera and ears Pachore et al. Arthroplasty (2019) 1:8 Page 6 of 9 In ochronotic cases, Cebesoy et al. [22] has recommended complete removal of the joint capsule. We speculated that complete capsular resection could increase the rate of dis- location postoperatively. Therefore, the capsule should be preserved and utilized for capsular closure. We did not find any complication with the use of the technique. The bone quality around the hip joint affects the stability of prosthesis. During reamerization, Cebesoy et al. [22] found poor bone quality at both the acetabulum and prox- imal femur irrespective of the patient’s age. In our cases, we noticed the bone quality of the proximal femur was in ac- cordance with the age of patients, but acetabulum wall was sclerotic, which was attributed to deposition of pigments in the deeper layers of articular cartilage (Fig. 4b). As a result, the cartilage loses its elasticity and become sclerotic [15]. In view of the matter, we advise to secure the cup with screws, because the sclerotic rim may impede the cup expansion. Before 1980, we did cemented THR because we did not had other choices, and in the rest of the hips we used cementless THR. Because the bone tissue is uncommonly in- volved, we were not suspecting any bone-ingrowth deficits that might affect stability of the cementless implants [15, 23]. In the present study, we didn’t observe instability, early loos- ening, subsidence, or protrusion problems on radiographs. Radiolucent lines, migration, or change in alignment were not observed on the acetabular socket. These factors are sug- gestive of stable implant with bone growth (spot welding). On femoral side, we did not find subsidence, radiolucent lines, or instability of femoral components (Fig. 6a, b, c, d, e, f, g and Fig. 7a, b, c, d). Long-term follows showed Fig. 6 Pelvis and both hips on X-rays. a preoperative anteroposterior view; b lateral view c anteroposterior view immediately after surgery; d anteroposterior view 5 years after surgery; e Lateral view 5 years after surgery; f anteroposterior view 10.5 years after surgery; g Lateral view 10.5 years after surgery Fig. 7 Pelvis and hips on X-rays. a an anteroposterior view preoperatively (left); follow-up X-rays after 2 years (uncemented ASR with S-ROM; right); b preoperative lateral view of left hip; c an anteroposterior view immediately after surgery (left) and follow-up after 2 years (right); d anteroposterior view at the final follow-up of 15.7 years (Uncemented ASR with S-ROM; right) and left hip (13.7 years; Pinnacle with Summit) Pachore et al. Arthroplasty (2019) 1:8 Page 7 of 9 that superior pain relief and successful restoration of hip function were achieved (mean follow-up time: 16.70 ± 6.82 years; range, 3 to 24 years) in patients with ochronotic ar- thropathy. We therefore conclude that both the uncemented and cemented total hip had long term survivorship. Our preference is to use a cemented THR in patients with poor bone stock or osteoporotic bone. Furthermore, in view of pa- tient’s stiff spine in present series, we strongly believe that in the early era of total hip arthroplasty in India, very little or no significance was attributed to the stiffness of spine and /or deformity of spine. We have operated on the patients in present series for a long time before the inception of concept of spinopelvic mobility and total hip arthroplasty. The con- cept of spinopelvic parameters/movements in relation to THR is new. So, we did not have preoperative lateral spino- pelvic-hip X-rays, nor sitting or standing lateral spine X-rays. In the early years, we had intraoperatively used manual jigs and eyeballing to achieve optimal component alignment with respect to patient’s anatomy and limb length. Versions/off- sets were attended independently to ensure optimal compo- nent positioning and a stable hip. In cemented hip, the principals of Charnley hip were followed to measure various angles. Recently, we used the principles of Scott Ranawat co- plannar test in uncemented surgery. Fortunately, there was no dislocation in these groups of patients, in spite of a 22- mm femoral head used. There is no specific medical treatment for alkapto- nuria, and hence all therapeutic approaches are symp- tomatic. In severe osteoarthrosis, total hip arthroplasty is the preferred treatment. Results from our series are con- sistent with the available literature [2, 22, 24–26]. The findings support reliability of THR in patients with ochronotic arthropathy. We hope the rationale behind the present series can guide the surgeons to establish the pre-operative diagnosis and to facilitate the intra-opera- tive procedures. No complications related to implant failure were detected after total arthroplasty, and our re- sults are compatible with patients who underwent pri- mary osteoarthrosis. Conclusion Primary hip arthroplasty is an effective and preferred treatment for alkaptonuric hip arthritis. The critical factor that directly influences the outcomes of total arthroplasty is surgeons’ acquaintance with the ochronosis. Through these cases we have attempted to provide tips pertinent to the establishment of the diagnosis of ochronosis and per- formance of THR for alkaptonuric hip arthritis. Those tips can help to lower surgical complications. Abbreviations DUS: Dried urine spot; HGA: Homogentisic acid; HHS: Harris hip score; THR: Total hip replacement Acknowledgements We acknowledge all the patients who participated in the study, nursing, paramedical staff. We also acknowledge the contribution of entire research team. Authors’ contributions JAP (Conceptualization; Data curation; Investigation; Methodology; Supervision; Writing–review & editing). VIS (Resources). SU (Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Resources; Supervision; Validation; Visualization; Writing – review & editing). KS (Resources). AS (Resources). AK (Resources). All authors read and approved the final manuscript. Funding Not applicable Availability of data and materials The data that support the findings of this study are available from [Shalby Hospitals India] but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of [Shalby Hospitals India]. Ethics approval and consent to participate The study was approved by the Scientific Review Committee and the institutional review board of the participating Health Service. Written Informed consent (about the surgical technique, risks and potential complications) was provided according to the Declaration of Helsinki and obtained from all participating patients. Consent for publication Informed consent was obtained from the patient’s for publication of their case records for providing evidence-based scientific literature for further research. Competing interests The authors declare that they have no competing interests. Author details 1Department of Hip Arthroplasty, Shalby Hospitals, Ahmedabad, Gujarat, India. 2Department of Knee, Shalby Hospitals, Ahmedabad, India. 3Department of Orthopaedics, NSCB Medical College, Jabalpur, MP, India. 4Department of Trauma, Joint Replacement and Minimal Invasive Surgery, Shalby Hospitals Jabalpur, Jabalpur, Madhya Pradesh, India. 5Department of Knee and Hip Arthroplasty, Shalby Hospitals, Ahmedabad, Gujarat, India. Received: 22 March 2019 Accepted: 12 August 2019 References 1. Keller JM, Macaulay W, Nercessian OA, Jaffe IA. New developments in ochronosis: review of the literature. Rheumatol lnt. 2005;25:81–5. 2. Spencer JM, Gibbons CL, Sharp RJ, Carr AJ, Athanasou NA. Arthroplasty for ochronotic arthritis: no failure of 11 replacements in 3 patients followed 6-12 years. Acta Orthop Scand. 2004;75:355–8. 3. Collins EJ, Hand R. Alkaptonuric ochronosis: a case report. AANA J. 2005;73:41–6. 4. Borman P, Bodur H, Ciliz D. Ochronotic arthropathy. 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