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J Am Acad Orthop Surg
J Am Acad Orthop Surg
JAAOS
JAAOS
jaaos
The Journal of the American Academy of Orthopaedic Surgeons
1067-151X
1940-5480
Lippincott Williams & Wilkins Hagerstown, MD

39151178
JAAOS-D-23-01208
10.5435/JAAOS-D-23-01208
00003
3
004
Reviews
Review Article
Challenges of Hip and Knee Arthroplasty in Patients With Osteopetrosis
Beckers Gautier MD gautier.beckers@gmail.com

Mazy David MD david.mazy27@gmail.com

Vendittoli Pascal-André MD pa.vendittoli@me.com

Morcos Mina W. MD mina.wahbamorcos@mail.mcgill.ca

https://orcid.org/0000-0002-1783-5085
Massé Vincent MD vincent.masse@me.com

From the Department of Surgery, Hospital Maisonneuve-Rosemont, Montreal University, Montreal, QC, Canada (Dr. Beckers, Dr. Vendittoli, Dr. Morcos, and Dr. Massé), the Department of Surgery, CHU Sainte-Justine, Montréal, Quebec, Canada (Mazy), the Clinique Orthopédique Duval, Laval, QC, Canada (Vendittoli and Massé), and the Personalized Arthroplasty Society, Atlanta, GA (Vendittoli).
15 10 2024
13 8 2024
32 20 938945
13 12 2023
07 6 2024
01 7 2024
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.
2024
American Academy of Orthopaedic Surgeons
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Osteopetrosis is a rare metabolic bone disease, characterized by dysfunction of osteoclasts, resulting in increased bone density and brittleness leading to pathological fractures and bone deformities. Hip and knee osteoarthritis (OA) are common long-term complications in patients with osteopetrosis. Joint arthroplasty surgery remains an effective and recommended treatment for these patients with an end-stage OA because it provides favorable outcomes. However, in osteopetrosis, joint arthroplasty surgery carries an increased risk of complications, and specific preoperative and perioperative considerations are required to deal with the technical challenges related to the disease. The aim of this article was to review some of the key aspects of osteopetrosis, provide technical recommendations, and answer clinically relevant questions related to hip and knee arthroplasty surgery.

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pmcOsteopetrosis, also known as “marble bone disease,” is a rare genetic disease first described in 1904.1 Its incidence is 1 in 20,000 and 1 in 250,000 births for the autosomal dominant osteopetrosis (less severe form) and autosomal recessive osteopetrosis (“malignant” form), respectively.2 Men and women are equally affected. The disease is characterized by a dense and brittle skeleton originating from a bone formation and resorption imbalance.

To the authors' knowledge, the exact prevalence of total joint arthroplasty (TJA) in patients with osteopetrosis remains unclear. However, the overall number of TJA procedures continues to rise annually because of demographic shifts and a growing demand for improved quality of life and mobility.3 Although osteopetrosis is rare, it predisposes individuals to conditions such as osteoarthritis (OA) and fractures, often necessitating TJA. Performing joint arthroplasty surgery in this population poses notable challenges. Orthopaedic surgeons may encounter patients with osteopetrosis in their practice or emergency settings, yet literature offering technical surgical recommendations is limited.

This article aims to explore the key aspects of the pathology and technical challenges that surgeons may encounter during total hip and knee surgery.

Osteopetrosis Pathophysiology

Normal bone metabolism is dependent on a balance between osteoblast-mediated deposition and osteoclast-mediated resorption. Osteoblasts and osteoclasts derive from mesenchymal and hematopoietic stem cell lines, respectively.4 Communication between the two cell types occurs through receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin.5 The binding of RANKL to RANK on the osteoclast surface enables their activation and differentiation. Osteoprotegerin, contrarily, is secreted by osteoblasts and binds to RANKL, thus blocking RANK binding and preventing osteoclast activation and survival.2 Constant bone turnover derives from the balance and interactions between these factors. The sequence starts with osteoblasts sending the signal to activate osteoclasts, which then starts bone resorption. Osteoclasts have chloride channels coupled to H+ATPase channels, which, by acidifying the environment and secreting proteases, respectively, dissolve the bone matrix and digest the organic part of the bone tissue.6 This, in healthy bone, forms Howship lacunae, which are resorption cavities within the bone. After this, osteoblasts synthesize bone matrix again, recreating a microenvironment that promotes osteoclast activity. They also secrete factors that stimulate macrophages and granulocytes, as well as interleukins that influence osteoclast activity.7 The interaction and balance between osteoclasts and osteoblasts is, therefore, permanent and necessary for efficient bone remodeling.8

Osteopetrosis arises from mutations in at least 10 genes, all leading to a lack of acidification and osteoclast activity.2 The dysfunction of osteoclasts leads to an imbalance in bone formation and resorption, resulting in dense, deformed sclerotic bones.7 Consequently, the bones are more brittle and more prone to fracture.1 Moreover, the healing ability in osteopetrosis can be impaired secondary to bone remodeling dysfunction. Although a fracture callus is usually formed, it does not reach the haversian organization, even 1 year after the fracture, leading to the possibility of additional microfractures.9 Although nonunion is common, bone healing can still occur; however, the time required to achieve it is increased.10

Classification

There are three main forms of osteopetrosis:9Autosomal recessive osteopetrosis, also known as infantile malignant osteopetrosis. It presents soon after birth, has rapid progression, and is associated with high mortality within the first decade of life.

The intermediate form, also known as autosomal recessive osteopetrosis. It presents within the first decade of life and is associated with repeated fractures.

Autosomal dominant osteopetrosis, also known as benign osteopetrosis or Albers-Schönberg disease. It is the most common and the least severe form. Its onset is late and is associated with few symptoms and unchanged life expectancy.

Clinical Presentation

The severity and clinical presentation depend on the type of osteopetrosis. There are hematopoietic abnormalities such as thrombocytopenia and anemia with hepatosplenomegaly, secondary to bony overgrowth of marrow spaces that prevents hematopoiesis. Bone remodeling at the level of the skull foramina can also lead to cranial nerve dysfunction and visual impairment.11 In the benign form, life expectancy is normal, but because of bone brittleness, fractures are frequent, representing the most common orthopaedic complication of the pathology. Moreover, nonunion and malunion often occur, leading to progressive bone deformities, such as coxa vara after nonunion of femoral neck fracture.10 Osteomyelitis is another frequent presentation in patients with osteopetrosis. The incidence is approximately 10% and is more commonly seen in the mandible. It is caused by reduced bone blood flow resulting from increased bone density and neutropenia.12 The abovementioned alterations in normal bone homeostasis lead to early-age OA.13

Radiological Presentation

There is an increase in bone density and volume, resulting in a narrow or missing medullary canal (Figure 1). A “bone within a bone” appearance may be present (Figure 2). Owing to the absence of bone remodeling, progressive bone deformation, nonunion, and malunion may occur.10 Progressive development of coxa vara is common. There is an enlargement of the metaphysis of long bones, also known as “Erlenmeyer flask deformity.”14 In addition, the vertebral end plates will also gradually thicken, giving the typical image of rugger jersey spine on spine radiographs. Increased bone density leads to brittle bone and fractures, and/or their sequelae are often observed.

Figure 1 Anteroposterior and lateral knee radiographs demonstrating a patient with osteopetrosis. Increased bone density and complete filling of the medullary cavity can be seen.

Figure 2 Radiographs demonstrating typical “bone within a bone" appearance in a 75-year-old patient with osteopetrosis.

Medical Treatment

Regarding the medical treatment specific to osteopetrosis, bone marrow transplantation (BMT) is for malignant infantile forms.15 BMT involves replacing the patient's defective hematopoietic stem cells with healthy donor stem cells, which will differentiate into mature blood cells, including osteoclasts, within the host. Based on the genetic mutation causing the disease, a bone marrow transplant could, in some cases, be a curative treatment.16

High doses of calcitriol (administered orally or subcutaneously) and interferon gamma-1b interferons (administered subcutaneously) both increase osteoclastic resorption and are used for benign forms.17 To the authors' knowledge, their efficacy is highly patient-dependent and still widely debated. Preclinical gene therapy studies have also emerged in recent years, with encouraging results.18 While BMT may offer curative potential in some cases, currently, no definitive curative treatment exists. Improvements of medical treatments would increase the life expectancy of the most severe forms and, therefore, increase the need for arthroplasty surgery. As for the general population, joint arthroplasty surgery is considered the benchmark treatment of end-stage hip and knee OA not responding to conservative treatment.

General Considerations for Total Joint Arthroplasty

Bone deformities, multiple fractures, and dense bone will lead to poor joint congruence, cartilage degeneration, and, therefore, the development of OA.10,19-21 In patients with osteopetrosis with end-stage OA, TJA is an effective treatment with good outcomes.19,21 However, patients with osteopetrosis require specific preoperative, perioperative, and postoperative considerations. Because of the increased level of technical difficulties and potentially higher risk of complications, total joint arthroplasty in patients with osteopetrosis should be performed by experienced surgeons.

Preoperative planning is essential to anticipate any potential difficulties and to have the required instruments on hand. Because of increased bone density, drill bits, pins, and saw blades will be saturated with dense bone debris. Frequent cooling and thread cleaning or replacement will avoid thermal damage to the bone, increase penetration, and prevent instrument breakage. Additional batteries, drills, pins, and saw blades are required and should be part of the preoperative planning.12

Although patients with osteopetrosis have a higher incidence of osteomyelitis, they do not seem to be at an increased risk of periprosthetic infections when compared with the general population.22 To our knowledge, there is no particular antibiotic prophylaxis protocol recommended for osteopetrosis. According to the literature, longer surgical time should be expected, with an average of 5 hours for total hip arthroplasty (THA) and 2.5 hours for total knee arthroplasty (TKA).23 This prolonged surgical duration can be attributed to several factors, including the narrowness and obliteration of the femoral canal and the extreme hardness of the bone. Recreating the femoral canal necessitates the use of a burr, drill, and ream under fluoroscopic guidance, which is a time-consuming process. Although prolonged surgical time is associated with increased rates of periprosthetic joint infection in the general population, such association has not been confirmed for patients with osteopetrosis.22,24 Regarding the postoperative period, no particular precautions regarding weight bearing or physiotherapy protocols are needed for uneventful surgeries.

Total Hip Arthroplasty and Resurfacing

In a database analysis, Burke et al22 found no evidence of increased complications in patients with osteopetrosis, except for higher rates of intraoperative fractures. To avoid the latter, several recommendations can be followed.

The narrowness and obliteration of the femoral canal present an increased challenge. Extra caution is required when preparing these canals to prevent cortex perforation or fracture. In an obliterated canal, intraoperative fluoroscopy may be used.25 High-speed burr or power drills are usually needed to help create the femoral canal.25 Once the canal is opened, a Cannulated drill over a flexible rod can be used to progressively increase the canal diameter. Starting with small drill bits, the canal should be enlarged in small increments, making sure the drill does not get stuck or break in the canal. Adding a prophylactic cerclage cable around the femoral diaphysis before reaming should be considered. While we use this practice in most cases, it is important to note that we do not perform it systematically.

Benum et al26 developed a stem and a personalized guide system for intramedullary reaming of the femoral stem, successfully used in two patients. The disadvantage of this alternative lies in the difficulty of obtaining necessary equipment. Another important consideration is the type of femoral implants used. In very sclerotic bone, standard rasps cannot be used to create the proximal shape of the femoral stem. It is recommended to use short narrow stems to facilitate implant insertion and decrease the risk of canal perforation and calcar fracture.13 In patients with osteopetrosis, intraoperative femoral fractures are a frequent complication occurring in up to 44% of cases and narrower canal seems to be a risk factor (Figure 3).27

Figure 3 AP radiographs demonstrating a 71-year-old woman with osteopetrosis and left groin pain. A, Left hip OA and remote proximal femur osteosynthesis. B, Status after left cemented total hip arthroplasty (THA). C, 4 years later, after right THA. (D) Periprosthetic Vancouver C femur fracture 8 months after right THA surgery treated by open reduction and plate fixation.

Both cemented and noncemented stems have been used in patients with osteopetrosis.25,27-32 When an appropriate stem fit is difficult to obtain, noncemented implants may be at risk of inadequate initial and long-term fixation.33 When initial fixation is not optimal, switching to a cemented stem may be considered. Moreover, in osteopetrosis, even if the osteoblasts are capable of bone formation and healing, this process is slower than in the general population.10 However, cementing an implant in an area of sclerotic bone with very little good-quality cancellous bone raises the same concerns for definitive fixation because cement penetration in bone surface is minimal.34 Even if no clear recommendation is available, the use of polished, taper cemented stems in patients with osteopetrosis seems appealing to reduce the risk of fracture.

In cases of an obliterated canal, hip resurfacing remains an attractive option because it avoids the creation of a canal (Figure 4).21,35,36 It should be remembered that resurfacing is better suited for coxa valga deformities (Figure 5) because it places compressive stress on the implants, rather than coxa vara, which places greater tensile stress on the implants.37 The femoral head stem hole needs to be created over a guidewire with multiple Cannulated drill bits. We suggest using 3-mm to 8-mm drill bits (from Cannulated screws) progressing in 1-mm increments. Moreover, the femoral head bone should be “soft” enough to be prepared with the cylindrical reamer. Otherwise, with too much torsional torque, a femoral neck fracture may occur. In case of hip resurfacing failure (intraoperative or late), it is still possible to revise the implant with a standard femoral stem.38

Figure 4 Preoperative radiograph (left) demonstrating a 16-year-old patient with osteopetrosis treated with a left hip resurfacing at 16 years of age. Last follow-up radiograph (right) of the same patient, 7 years after surgery. She is very active and pain free.

Figure 5 Example of an ideal case of resurfacing surgery. Anteroposterior pelvic radiograph showing a coxa valga deformity in a young patient with osteopetrosis.

Over the past decade, the authors have favored THA over hip resurfacing, primarily due to the potential complications associated with metal-on-metal implants, such as adverse local tissue reactions or pseudotumors and metallosis. However, it still remains a viable alternative in carefully selected cases where the femoral canal is fully obliterated, the acetabulum diameter is larger than the femoral head diameter (presence of erosion), the femoral neck is not in varus, and there is limited acetabular dysplasia.21

On the acetabular side, several reports with both cemented and noncemented implants have been published, although the best option remains unknown.26,29,33 Again, the local bone quality plays a major role in the decision process. Some patients may have normal subchondral bone or it may be hard like marble. In a retrospective study on 9 THA patients by Siljander et al, the rate of intraoperative acetabular fracture, mainly during final noncemented implant impaction, was found to be notable with the occurrence of 5 events (56%).27 Note that this trend is not found in the rest of the literature. To reduce this complication, gentle line-to-line reaming is recommended.27 The use of acetabular screws is frequent in patients with osteopetrosis, but also challenging.23,39 In fact, the placement of these screws requires multiple drill bits, the use of a tap to prepare the threads, and possibly the need to change the screw before full insertion if torsional fatigue occurs. In very hard bone, one should opt for a cemented polyethylene cup with multiple anchor holes.

Patients with osteopetrosis do not seem to be at increased risk of dislocation. Postoperative instructions are the same as for patients with OA.22

Total Knee Arthroplasty

Similar to THA, the increased density and brittleness of osteopetrotic bone require some technique modifications in TKA. Numerous case reports describe the occurrence of iatrogenic intraoperative fractures in TKA.12,32,40 However, a national database analysis by Burke et al22 on 972 TKA procedures in patients with osteopetrosis reported no notable increase in intraoperative periprosthetic fractures when compared with patients without osteopetrosis. It is recommended to use extramedullary guides, computer-assisted surgery, or robotic assistance to avoid passing through the medullary canal.19,23 The increased bone density makes pin insertion (for cutting guides or navigation/robotic tracker) difficult. Because of the minimal bone remodeling of osteopetrotic bone, there is a higher risk of pin hole stress fracture. Smaller tracker pins in the metaphyseal region would be favorable. Another interesting option is patient-specific instruments. The latter eliminates the need for intramedullary guides, reduces the number of pins used to fix the cutting jig, and reduces the number of bony recuts.12,41 When using pins, some recommend their advancement at reduced speed along with physiological liquid cooling to diminish the risk of thermal injury and necrosis while others argue that low-speed pin insertion is virtually impossible in patients with osteopetrosis.12,19 The use of a predrill might also help.

Tibial baseplates with long keels should be avoided. In sclerotic bone, tibial keel punch should not be used. A speed burr or a saw blade can be used to create the keel slots. Posterior-stabilized femoral implants require preparation of the intercondylar box. Additional bone cuts expose the patient to an increased risk of iatrogenic fractures. We, therefore, favor cruciate-retaining or medial-pivot designs.

Because of the small amount of cancellous bone and the increased risk of iatrogenic fracture during impaction, cemented implants are recommended.12,19,23,32 Only one publication reporting noncemented TKA complicated with an iatrogenic tibia fracture was found.40 To facilitate cement interdigitation, performing multiple drill holes of the bone surfaces is recommended.19

Resurfacing the patella remains controversial.42 Although in most published case reports, the patella was left unresurfaced, the literature is scarce on whether patella resurfacing in patients with osteopetrosis should be performed.12,19,23 Because of the technical challenge in very dense bone and the theoretical risks of fractures, we do not recommend patella resurfacing, although it remains at the surgeon's discretion.19

Conclusions

Osteopetrosis is a rare disease, but an increasing number of patients with the benign form require hip or knee arthroplasty. TJA gives excellent results, but the metabolic changes of this pathology require specific surgical considerations. New arthroplasty technologies enable us to better plan and anticipate any difficulties that may arise. Therefore, it seems appropriate for patients with osteopetrosis to be referred to specialized centers that have necessary equipment. The latter will help to minimize complications, improve patient outcomes, and increase implant survival rates.

Unrestricted Grants from Johnson and Johnson, Smith and Nephew, Stryker and Zimmer, paid to my institution.

None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Beckers, Dr. Mazy, Dr. Vendittoli, Dr. Morcos, and Dr. Massé
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