Total Joint Arthroplasty in Ochronotic Arthritis of Lower Extremities

Abstract

Background

Ochronotic arthropathy is an inherited metabolic disease manifestation of alkaptonuria (AKU), commonly involving the spine, knees and hips. End-stage ochronotic arthritis (OcA) requiring total joint arthroplasty (TJA) is uncommon, with only few case series being described in English literature.

Materials

The objective of current study is to share our surgical experience of treating four patients with end-stage arthritis, who underwent eight TJAs of the lower extremity (5 hips and 3 knees) in whom an intraoperative diagnosis of ochronosis was suspected after surgical exposure of the operated joint. We describe the intraoperative challenges faced during surgical treatment, diagnostic tests and mid-term follow-up results.

Results

Four AKU patients (3 females) with end-stage OcA of the hips and/or knees, underwent eight total joint replacement surgeries, under neuraxial anesthesia in the majority. All patients were either in their late fifties or sixties at the time of their index TJA. We encountered one case each of peri-prosthetic fracture, medullary canal perforation and early prosthetic infection, all of which were successfully treated. The mean follow-up was 5.2 years (1–10 years) and all patients had satisfactory clinical outcomes at the last follow-up.

Conclusions

The surprise intraoperative diagnosis of OcA, along with associated juxta-articular sclerosis or osteopenia can lead to intra-operative complications. These complications when addressed appropriately did not adversely affect the clinical outcomes of TJA for end-stage hip and knee arthritis, at a medium-term follow-up.

Introduction

Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism, due to defective gene coding for homogentisic acid (HGA) oxidase enzyme on chromosome 3q, leading to deposition of HGA in various collagenous tissues like pinna, sclera, articular cartilage, heart and kidneys [1, 2]. HGA deposition gives the characteristic ochre or brownish black pigmentation to the soft tissues, a condition known as ochronosis. Alkaptonuria triad consists of dark-colored urine, ochronosis and ochronotic arthropathy (OcA). This extremely rare, autosomal recessive disorder has a prevalence ranging from one in a million to 2.5 million population and been reported in Europe, the Middle East, and India [2–6].

HGA deposits make the soft tissues rigid and pigmented, leading to progressive degeneration of multiple intervertebral disks, hyaline cartilage, ligaments and tendons. This condition is called as ochronotic spondylarthropathy [7]. Ochronotic arthritis commonly involves the spine initially, but as the disease progresses, large weight-bearing joints like knees and hips get affected [8–10]. There is no specific treatment for alkaptonuria although nitisinone, ascorbic acid, and low-protein diets have been used to slow down the progress of ochronosis [2, 11].

Total joint replacement surgery is mainly performed for end-stage OcA of large joints of lower extremities (knees and hips) although on rare occasions, total shoulder and total elbow joint arthroplasty have been described too [11, 12]. Ochronotic arthropathy is quite commonly detected by orthopedic surgeons as an intraoperative surprise when they encounter ochre or brownish black pigmentation of exposed joints and soft tissues, while performing joint replacement arthroplasty. However, challenges do exist in diagnosing OcA due to the non-familiarity in treating this extremely rare condition [2, 8, 13, 14].

A review in English literature, where a minimum of four TJAs have been performed in each study, revealed only seven such studies [1, 4–6, 12, 15, 16]. The salient features of previous such studies have been summarized to create awareness among arthroplasty surgeons who can encounter this rare condition at some stage of their surgical careers (Table 1).

Table 1.

Literature review describing salient features and clinical outcomes

Author Year, Country	Case series	Sex	Total number of TJAs/site	Follow-up	Spinal changes	Anesthesia	Intraoperative findings	Postoperative Complications/death
Phornphutkul 2002, USA	26/58 chronic joint pain	Female-12 Male-14	29 TJA, THA-10, TKA-17, 2 shoulders	–	–	–	–	More than three TJAs—eight, 50% TJAs by the age of 55 years, Disease in men more severe
Spencer 2004, UK	Three cases	All females	11 TJA, THA-6, TKA-3, Elbow-2 Shoulder-1	6–12 years	Yes-all	–	–	One hip dislocation at 12 years, One patient died at 6 years (cardiac cause)
Rajkumar 2020, India	16 cases	4 Females 12 Males	27TJAs, 12TKA, 15THA	1–12 years	Calcified Disks-13	General-18 Regional-9	THAs: Hardinge approach Synovectomy-all TKAs Patella resurfacing-5	Death-2 (unrelated causes) Deep infection-1, Aseptic acetabular loosening-1
Pachore 2019, India	10 cases,	6 Males 4 Females	12 TJA 12 THA	3–24 years	Yes-all	–	More blood loss, all Acetabular cup screws IM canal drilling hard	Death-1 (16 years, breast cancer) Complications—Nil, (but right femoral peri-prosthetic plate fixation seen on illustration)
Al-Ajlouni Jordan, 2020	Five cases	Male-2 Female-3	8 TJA 4 THA 4 TKA	2–10 years	Back pain-4	All—spinal anesthesia	Osteoporosis, hence TKA with long tibial stem used	Complications-Nil All done with regional anesthesia
Ulucay Turkey, 2013	Two cases	Both males	5 TJA 3 TKA 2 THA	2 years	Back pain-1	Both general anesthesia	Long stem femur-1 Long stem tibia-1	Aggressive synovectomy, blood loss Recurrent effusions both knees
Ilyas Saudi Arabia, 2020	One case	Male 45 years	4 TJA 2 THA 2 TKA	12 years	–	–	Tissue pigmentation	Complications-Nil
Present study 2022, India	Four cases	Mean age > 60 years, Male-2 Female-2	8 TJA 5 THA 3 TKA	1–10 years Mean-5.2 years	Yes-all	Regional-7, General-1	Protrusio acetabuli-1 Acetabular osteopenia-2 Femoral osteopenia-2	Periprosthetic fracture-1 Femoral IM canal breach-1 Deep infection-1, All were successfully treated Death-1 (at 10 years, cardiac cause)

Only case series with a minimum of 4 or more TJAs have been included

The surgical complications noted in earlier studies include difficulties in exposure, bleeding, infection, deep cup placement, aseptic loosening and peri-prosthetic fracture [5, 6, 17]. Although OcA can be commonly misdiagnosed as ankylosing spondylosis or osteoarthritis, the surgical outcomes following TJAs for OcA are comparable to arthroplasty results for primary hip and knee osteoarthritis, provided proper precautions are taken [14, 18].

We present our case series of four patients, who successfully underwent eight lower-limb TJAs for the treatment of end-stage OcA, along with significant intraoperative findings, surgical challenges, management of complications and follow-up outcomes.

Materials and Methods

The local research ethics committee deemed that institutional review board approval for this retrospective case series was not necessary. The compliance with ethical standards described in 1964 Declaration of Helsinki and CARE guidelines was followed. A total of five patients with AKU/ochronosis, who had undergone orthopedic surgeries by the authors, at three centers, between 2011 and 2016, were identified. Informed consent was taken from all patients.

Four AKU patients (three females) with end-stage OcA of the hip or knee joints, who underwent their first TJA between 2011 and 2016, were included in the current study. One case of lumbar discectomy in a known case of AKU was excluded. None of these four patients, who underwent elective joint replacement surgeries, reported a preoperative diagnosis of AKU/ochronosis, at the time of their first surgery. All patients were either in their late fifties or sixties at the time of their index TJA, when ochronosis was first suspected intraoperatively. A detailed general physical and systemic examination along with radiological survey of the lumbar spine, pelvis and affected hip/knee joints was done in all cases. Comprehensive preoperative blood tests, ECG and echocardiogram, along with urine analysis and urine HGA testing were done in all cases. Postoperatively, histopathologic examination of the resected bone and excised soft tissues was undertaken for confirmation of the definitive diagnosis in all cases (Fig. 1).

Fig. 1.

L–R, a Brown pigmentation of sclera (Osler’s sign) and nose, b urine discoloration on standing and c histopathology showing tissue pigmentation along with multinuclear giant cells

Results

Of the four patients, one died at a long-term follow-up of 10 years due to unrelated cause. The mean age at the time of first TJA was 60.5 years (56–68 years). The mean mid-term follow-up was 5.2 years (1–10 years) Demographic variables, history, clinical assessment, anesthesia, surgery, significant intraoperative findings, complications and medium-term follow-up are summarized in Table 2.

Table 2.

Current study detailing the clinical features, anesthesia, intraoperative findings and outcomes of TJR surgeries

Case	Age/sex	Site	Symptom duration	Family history	Spine pain	Anesthesia	Disease detection	Significant operative findings	TJR (surgeon)/approach	Outcome & follow up
1a	60 years Male	Right Hip	Pain, limp 3 years	Yes	Yes	Epidural & Spinal	Operative	Acetabular osteopenia	Hybrid THA (PB) Posterior	Satisfactory 8 years
1b	63 years Male	Left Hip	Pain, limp 2 years		Yes	Epidural & Spinal		Acetabular osteopenia	Uncemented THA (BR) Posterior	Satisfactory 5 years
2	68 years Female	Left Hip	Pain, limp 2 years	Nil	Yes	Spinal	Operative	Protrusio acetabuli, Femoral & acetabular Osteopenia	Cemented THA (PB) Posterior	Satisfactory 10 years
3	56 years Female	Left Knee	Pain, Varus 2 years	Yes	Yes	Spinal	Operative	Post-implantation peri-prosthetic fracture	Cemented TKA (PB) Medial parapatellar	Satisfactory 7 years
4a	58 years Female	Right Knee	Pain, Varus 3 years	Yes	Yes	Spinal	Operative	Significant juxta-articular osteopenia	Cemented TKA (DI) Medial parapatellar	Satisfactory 7 years
4b	61 years	Left Knee	Pain, Valgus 2 years	Yes	Yes	Spinal & nerve block		Femoral cortical breach by IM jig Long femoral stem extender used	Cemented TKA (DI) Medial parapatellar	Satisfactory 6 years
4c	61 years	Left Hip	Pain, limp 1 year	Yes	Yes	Spinal & nerve block		Sclerotic acetabulum No defect	Uncemented THA (DI), Posterior	Satisfactory 5 years
4d	67 years	Right Hip	Pain-2 years lumbar scoliosis	Yes	Yes	General anesthesia		Early deep infection, Joint lavage with liner exchange, intravenous antibiotics	Uncemented THA (DI) Posterior	Satisfactory 2 years

Clinical assessment: A detailed history revealed progressive hip or knee pain, limp and restricted mobility preceding the surgery. Backache was observed in all patients, well before the onset of severe hip or knee symptoms. One patient had progressive degenerative scoliosis, in whom her final TJA was performed under general anesthesia. Family history of ochronosis was retrospectively identified in three of the four patients. All patients had history of dark pigmentation of urine on exposure to air. Sclera was pigmented in all patients, while two patients had palpable subcutaneous nodules. None of the patients were on any specific treatment for the disease other than symptomatic treatment for musculoskeletal symptoms. Routine blood tests including inflammatory markers, electrocardiogram and echocardiography were normal in all cases. Routine urinalysis showed urine pigmentation on standing and urine HGA positivity (homogentisic aciduria) in all cases. Salient radiologic findings revealed osteoarthritic changes of the affected joints with sclerotic articular surfaces and juxta-articular osteopenia. In addition, calcification of multiple intervertebral disk spaces was noticed in the lumbar spine or pelvis radiographs in all cases. However, the sacroiliac joints remained unaffected (Figs. 2, 3, 4).

Fig. 2.

X-ray Pelvis with hips-AP views a showing bilateral hip arthritis with left protrusio acetabuli (Case 1). b Right Hybrid THA with deep cup placement, left hip arthritis and intradiscal calcifications in lumbar spine (Case 2) c shows bilateral THA at 5-year follow-up

Fig. 3.

L–R (Case 3) a Intra operative photograph showing brownish black pigmentation of articular surfaces after surgical exposure for left TKA. b Intraoperative fluoroscopic AP view and c lateral view showing iatrogenic fracture of lateral femoral condyle after final implantation

Fig. 4.

L–R (Case 4) a X-ray Pelvis with hips-AP views showing right hip arthritis with uncemented left THA in situ. b Postoperative X-ray after right uncemented THA. c Excised ochronotic femoral head. d Bilateral TKA with femoral stem extender on left knee following distal femoral cortical breach, at 5-year follow-up

Anesthetic considerations: All TJAs, except one, were performed under neuraxial anesthesia. Postoperatively, all patients were monitored in surgical high dependency unit and none required intensive care support. Packed red cell transfusions were done following four surgeries (50%).

Surgical Considerations

Total hip replacement: All hips were operated in the lateral decubitus position, through a posterolateral approach. Ochronotic pigmentation of hip capsule and articulating surfaces was noticed in all five hips (Fig. 4b). Extensive extra-articular pigmentation of the soft tissues was noted in one patient. This patient underwent cemented THA because of poor bone quality detected intraoperatively. The remaining two patients who underwent bilateral THA, had uncemented acetabular shell fixation in their sclerotic acetabular cavities, augmented with screws. Both patients had difficult initial reaming of the acetabular cavity. Further reaming was stopped when minor acetabular floor breaches were noted in two hips. One patient, who had deeper placement of the acetabular cup, underwent an uneventful hybrid THA with a cemented femoral stem (Fig. 2b). On the femoral side, uncemented fixation was used in the remaining three hips. (Figs. 2, 3) Post-operatively, none of the patients had any nerve palsy, dislocation or any significant limb length discrepancies. The mean preoperative modified Harris hip scores (mHHS) was 18 (range 16–22) and the mean postoperative mHHS was 80 (76–82). The hip scores improved significantly in all cases.

We encountered one early deep infection with Klebsiella pneumoniae and it was successfully treated with arthrotomy, joint irrigation, retention of implants and antibiotic therapy with intravenous ertapenem and ciprofloxacin for 3 weeks, followed by oral ciprofloxacin therapy for further 3 weeks. There was no further episode of infection at a 2-year follow-up and the patient remains under further surveillance.

Total knee replacement: Three knees (two patients, one bilateral) were operated in the supine position, under tourniquet control, by a midline anterior incision and medial parapatellar arthrotomy. Black pigmentation of the articular surfaces, sclerotic menisci and patellar tendon insertion was noticed in all cases. In all knees, the bone quality underneath the sclerotic articulating surfaces was osteopenic. All TKAs were cemented, of posterior cruciate sacrificing (PS) design, with no patellar resurfacing. (Figs. 3, 4) Mean knee society scores (2011KSS) in the two patients improved from 24 (18–30) to 88 (86–90).

Complications: We encountered two complications while performing TKA. First, a distal medial femoral cortical breach while introducing the femoral intramedullary (IM) jig. The breach was confirmed by palpation and intraoperative fluoroscopy before proceeding with an uneventful cemented TKA using a long femoral stemmed prosthesis, with a satisfactory outcome at a 5-year follow-up (Fig. 4d).

Another patient sustained a stable undisplaced periprosthetic fracture of the lateral femoral condyle after successful cementation of prosthesis. This occurred during trial reduction with a larger tibial polyethylene insert. Percutaneous cancellous screw fixation failed to achieve compression of the fracture and fracture fixation was abandoned. Final fluoroscopic imaging confirmed a stable undisplaced fracture pattern (Fig. 3b, c). Patient was mobilized with graduated protected weight-bearing till 3 months, followed by full weight-bearing after confirming fracture union. Patient had stable, pain-free mobility and no evidence of loosening, at a 6-year follow-up.

Rehabilitation: Post-operatively, rehabilitation was personalized to each patient based on the bone quality, type of implant used or complications encountered. Uncomplicated cemented TJAs were mobilized full weight-bearing from immediate postoperative period. Uncemented TJAs had an initial period of protected weight-bearing for 6 weeks, followed by full weight-bearing thereafter.

Discussion

Ochronotic arthritis, a manifestation of long standing AKU, leads to systemic deposition of HGA and progressive degeneration of not only musculoskeletal structures, but also tissues like sclera, pinna, heart and kidneys [19]. So far no cure exists for AKU although emerging evidence in recent trials confirm the beneficial effects of low-dose nitisinone, ascorbic acid and tyrosine-restricted diet in slowing down the progress of AKU [2]. A flowchart as to how to navigate around the AKU/OcA patient has been presented (Table 3).

Table 3.

Flowchart showing the manifestations, presentation, diagnosis, treatment and surgical considerations while navigating the alkaptonuria/ochronotic arthritis patient

Ochronotic arthritis can present to orthopedic surgeons in different clinical settings. In our study, OcA was suspected intraoperatively in all patients, by three different operating surgeons, at the time of their index TJA. Ochronosis was confirmed by scleral pigmentation (Osler’s sign), urine pigmentation on standing due to presence of urine HGA, along with histopathological examination of excised tissues. Benedict’s test, ferric chloride and ammoniacal silver nitrate tests have also been described for by confirming the presence of reducing agent (HGA) in the urine. Serum HGA level estimations can also be performed where facilities exist. Synovial fluid aspiration can demonstrate floating black particles (ground pepper sign) [2]. Confirmatory tests for diagnosis of AKU are chromatographic, enzymatic, or spectrophotometric determinations of HGA. In hindsight, we feel that the preoperative radiologic findings of extensive lumbar disk calcifications should have drawn our attention to this rare condition, thus avoiding missing the diagnosis. Second, a known AKU/ochronosis patient can present to the same or different surgeon for subsequent TJAs as observed in the remaining four arthroplasties of current study.

Although this condition affects all races and both sexes equally, the severity of disease intensifies after the age of thirty years, especially in men, leading to early skeletal manifestations, followed later by renal or cardiac manifestations [20, 21]. The condition does not increase mortality or morbidity due to its multisystem involvement [22]. Wu et al. described the musculoskeletal triad of AKU: arthropathy, osteopenia and tendinopathy [21]. The ochronotic deposits not only result in crippling arthritis requiring TJAs, but can also cause tendon tears, necessitating repairs and fractures that need internal fixations, including periprosthetic fractures [18, 20, 22, 23].

TJA is an effective option for end-stage OcA and it can improve functional outcomes and quality of life of the affected patients [5]. The exact number of knee replacements ever done for OcA is unknown, but it is likely to be low given the rarity of the condition and the limited case reports in literature. Carrier described the first case report of bilateral hip and knee arthroplasties in the same patient [24].

Life-table analyses have shown that joint replacement surgeries for ochronotic arthritis are performed at a mean age of 55 years [23]. This is in agreement with our study where all patients were above the age of 55 years at the time of first surgery, and the mean age at first TJA was 60.5 years. Three of the four patients came from a rural background and presented with considerable delay before seeking surgical treatment.

hvIf the isolated cohort study of 14 hip replacements for ochronotic hip arthritis by Pachore et al. is excluded, the remaining case series accounted for 62 TJAs (30 patients) of which 59 TJAs (95.1%) were performed for either the hip or knee joint (Table 1). Four patients in our study successfully underwent eight arthroplasties for end-stage ochronotic hip or knee arthritis, with significant reduction in pain, improved joint function and satisfactory clinical outcomes at a mean mid-term follow-up of 6.2 years (Table 2).

Total Hip Arthroplasty

Poor bone quality of the acetabulum and proximal femur, irrespective of patients age, has been reported earlier by Cebesoy et al. [17]. Cemented fixation of the hip components may be used when the bone quality is poor and precludes the use of press-fit uncemented implants. We performed cemented and hybrid THA in one patient each, with excellent outcomes in both.

Pachore et al. noticed the bone quality of the proximal femur was in accordance with the age of patients, but acetabular wall was sclerotic. They secured acetabular cup fixation with screws, as the sclerotic rim impeded cup expansion. Although there is no mention of peri-prosthetic fracture in their case series, an illustrated radiograph showed long uncemented femoral stem with peri-prosthetic plate and cable fixation [6]. In agreement with earlier studies, whenever the bone quality was sclerotic and a good stable press-fit fixation was obtained, and uncemented hip prosthesis was implanted in the remaining three THAs in the current study.

Preoperative history of ochronosis or associated blackish discoloration of the acetabular cavity should alert the operating surgeon to exercise utmost care during acetabular reaming. Hip surgeons should anticipate not only the difficult reaming of sclerotic acetabular surfaces, but also the osteopenia underneath them. This may potentially help in avoiding deep cup placement or breaches of the acetabular floor that we encountered.

Total Knee Arthroplasty

Both patients underwent cruciate sacrificing cemented TKAs with no patellar resurfacing, in view of severe arthritis and osteopenic bone quality. Cementless prosthesis can also be used in eligible candidates, as bone ingrowth is not affected in this disease [8–10, 19]. Outcomes following TKA are good irrespective of cemented or cementless prosthesis use [25]. Like in the hip, surgeons performing knee arthroplasty should also anticipate the peculiar combination of “sclerotic articular surfaces with underlying osteopenia”, in order to avoid complications that we faced. There was a higher incidence of intra-operative complication while performing the first TJR for that particular patient. This could possibly be multifactorial: sudden intraoperative diagnosis, surgical inexperience with anticipating intraoperative challenges due to Wu’s “musculoskeletal triad of AKU” and lastly, performing the initial surgery on the more severely affected joint. This has been described earlier by Patel who recommends the use of cemented implants in such cases [26].

Anesthetic Considerations

Cardiovascular involvement is a serious consequence of alkaptonuric ochronosis and it has been reported that approximately 40% of alkaptonuric patients will eventually develop cardiovascular disease by their fifth decade [27]. Hence, spinal anesthesia may be safe in view of coronary and cardiac valvular involvement, but spinal degenerative changes may lead to difficult or complicated regional anesthesia [28]. Ochronotic spondyloarthropathy resembles ankylosing spondylosis in many ways, although with subtle differences [29]. Hence, difficult spinal anesthesia should be anticipated and there should be no hesitation to switch to general anesthesia [8, 15]. In the current study, seven surgeries were performed with regional anesthesia safely. One THA was performed under general anesthesia due to failed spinal anesthesia in view of progressive degenerative lumbar scoliosis; the previous three TJAs in this patient had been performed successfully under regional anesthesia. Increased perioperative blood loss has to be anticipated and adequate arrangements should be made for packed red cell transfusions should the need arise. Patel described excessive bleeding up to 1150 ml, requiring delayed drain removal [28]. In the current study, none had excessive blood loss requiring multiple transfusions. This may be related to performing less-aggressive synovectomies during TJAs.

One patient died due to cardiac cause, unrelated to her surgery ten years after successful THR. She had recurrent postoperative E. coli urinary infections and refused to undergo endoscopic removal of urinary bladder stones before contralateral hip surgery. Such decline of subsequent TJA has also been previously reported by Ulucay et al., where their patient declined contralateral TKR procedure despite having successful outcomes after the first surgery. Their patient had extensive blood loss, multiple blood transfusions and intensive care treatment, following aggressive synovectomy [15]. Due to multiple system involvement, the ochronotic patient may require surgeries not only for skeletal manifestations, but also for cardiac valvular disease and nephrolithiasis [22].

Complications

Operative complications while treating OcA are sparsely mentioned in view of the rarity of this surgical condition. These include difficult exposure, bleeding, infection, deep cup placement, aseptic loosening and peri-prosthetic fractures [5, 6, 17]. Rajkumar et al. have described one each of deep hip infection and aseptic loosening of the acetabular component in their series of 15 patients, both necessitating revision hip surgeries with successful outcomes eventually [5]. We encountered two specific complications. One case each of peri-prosthetic fracture, medullary canal perforation, both of which were successfully treated with satisfactory outcomes at minimum 5-year follow-up. The isolated case of deep hip infection was successfully treated by arthrotomy, joint lavage, implant retention and antibiotic therapy, with satisfactory outcomes and no recurrence of infection at 2-year follow-up. The higher incidence of juxta-articular osteopenia may be multifactorial, three of the four patients who had severe disease before their index surgery, had higher mean age at first presentation and hailed from agrarian households. The last patient had progressively severe disease, eventually requiring bilateral total hip and knee arthroplasties.

Tips to prevent complications: Awareness of the potential complications as well as anticipating the “osteopenia underlying the sclerotic joint surfaces” by the treating orthopedic surgeon, both in hip and knee surgery, could possibly reduce the risk of complications. In hindsight, we feel peri-prosthetic femoral condyle fracture could possibly have been averted by accepting a thinner polyethylene insert, but doing so may have compromised joint stability. Such peri-prosthetic fractures following trial reduction have been described in literature, especially with the use of PS design femoral implants that employ the femoral box cut. Also, utmost care should also be taken during intramedullary femoral jig placement through sclerotic bone as inadvertent unidentified perforations could potentially lead to neurovascular injuries or errors while performing the distal femoral cut, causing femoral component malposition.

Strengths and limitations: Although there are many isolated case reports of joint replacement surgeries for ochronotic arthritis, there exist very few case series in English literature that have studied 5 TJAs or more. The limitation of our study is that it is a retrospective, multicentric, case series that lacks follow-up for 10 years or more. Interestingly, despite the perioperative surgical challenges encountered, none of the seven TJAs had any adverse functional outcomes at a minimum midterm follow-up of 5 years. We agree that although ochronotic arthritis does not increase mortality, but it does produce considerable morbidity due to its multisystem involvement [30].

Future directions: Treatment options in AKU are limited [16]. A low-protein (tyrosine and phenylalanine) diet and ascorbic acid supplementation have shown to reduce urinary HGA excretion with reversal of bone abnormalities. [31] Nitisinone is the first disease-modifying drug approved by European medicine agency in 2020 for adults with alkaptonuria [32]. This drug has been shown to safely and effectively reduce HGA production and urinary excretion, with significant clinical improvement in reducing backache, tendon tears as well as beneficial changes in serological/urinary biomarkers of bone and cartilage remodeling [32, 33]. Physiotherapy and nonsteroidal anti-inflammatory drugs can limit symptoms with no effect on disease progression [32]. In end-stage cases of OcA, surgical intervention through total joint replacement represents the best treatment available [2, 5, 6].

Conclusions

End-stage ochronotic arthritis of hips and knees can spring an intraoperative surprise for lower-limb arthroplasty surgeons due to the rarity of this inherited metabolic disease. The authors recommend utmost care among arthroplasty surgeons while handling ochronotic tissues, anticipating potential complications throughout the surgery and preventing adverse outcomes by taking necessary intraoperative corrective measures. Perioperative complications during TJAs are not uncommon, and if treated well, they can lead to satisfactory clinical outcomes at a mid-term follow-up.

Funding

The authors received NO financial support for the preparation, research, authorship and publication of this manuscript.

Data availability

Not applicable, available on demand.

Declarations

Conflict of interest

The authors declare that they do not have conflict of interest for this manuscript.

Ethical Approval

Ethical committee waiver for retrospective case series.

Informed Consent

We declare that there is no information in the submitted manuscript that can be used to identify patients.