Biopsies can be considered as the ultimate diagnostic tool in the diagnostic flowchart of skeletal lesions. As the ultimate step, it should always be preceded by an accurate clinical and radiological assessment.
The goal of the biopsy procedure is to obtain a tissue sample that permits to obtain a diagnosis with the minimum risk to the patients. Due to this, minimally invasive approaches such as percutaneous needle biopsies are currently preferred to surgical ones as the first line. Image-guided biopsy procedures have been performed increasingly frequently in recent decades, due to the reduction in complications and increased precision compared to blind procedures.
2. Biopsy: General Concepts
A biopsy can be performed surgically (open biopsy) or by a percutaneous approach (closed biopsy). An open biopsy presents several disadvantages, including increased procedure times, risks inherent to the surgical procedure (e.g., wound healing and infections), increased costs and the need for a hospital stay and deep anesthesia 
Skeletal biopsies are nowadays performed with the percutaneous approach, while open biopsies are generally performed after a non-diagnostic closed biopsy, especially in the extremities 
. A percutaneous skeletal biopsy includes fine needle aspiration and also a core needle biopsy.
Imaging guidance offers additional value to the biopsy procedure in terms of the efficacy and safety compared to blind bone samples in all cases.
Fluoroscopy has been used as the main imaging tool for skeletal biopsy guidance for decades. Subsequently, with the introduction of cross-sectional imaging, computed tomography (CT) has been proposed as a guidance for bone biopsies. Nowadays, CT-guided biopsies are the preferred technique for all skeletal sites with increased advantages compared to fluoroscopy, particularly in the spine and pelvis 
. In all skeletal regions, the precision and safety provided by CT are significant benefits.
In 1930, Martin and Ellis published a presentation of technical percutaneous procedures used to secure tissue from suspected neoplasms for a histological evaluation by needle puncture and aspiration 
. This preliminary series included different body districts sampled, including several skeletal regions (the mandible, humerus, scapula, humerus and pelvis). The percutaneous procedures performed on bone resulted in successful histological diagnoses including bone sarcomas, chondrosarcomas, spindle cell sarcoma and osteogenic sarcoma 
One year later, Bradley and colleagues reported 35 cases of bone tumors successfully diagnosed by percutaneous needle aspiration 
. These procedures, performed almost 100 years ago, represent the progenitor of modern skeletal biopsies, and in some way, of the entirety of percutaneous musculoskeletal interventional radiology. In the following decades, bone biopsies were associated with imaging guidance, firstly fluoroscopy, to increase precision and safety. Later on, together with the increased availability of cross-sectional imaging tools, skeletal biopsies were increasingly associated with CT guidance, gaining additional potentiality and nonetheless being recognized as a procedure for medical radiologists 
4. Image Guidance
A skeletal biopsy can be performed under fluoroscopic, CT or ultrasound guidance. CT guidance is currently the most used tool for the imaging of bone biopsies, permitting to sample almost all skeletal sites in a safe manner.
Fluoroscopy-guided skeletal biopsies still have a role, usually where CT guidance is not available. This procedure is generally performed in surgical settings by orthopedics. This procedure is particularly indicated for long bones in the extremities, where the precision of CT guidance is not strictly necessary 
An ultrasound-guided skeletal biopsy is a very interesting tool, offering the advantages of a real-time evaluation and an accurate adjacent soft tissue assessment, with particular regard to neurovascular bundles 
. Nonetheless, this procedure is particularly indicated when a cortical disruption is present, aiding the ultrasound waves to bone lesions/neoplasms, and/or in the case of superficial bone regions such as the ribs 
. In these cases, the diagnostic accuracy and safety are reported to be comparable with CT-guided biopsies.
The feasible and suggested imaging guidance techniques depending on the skeletal site and the lesions’ radiologic patterns are summarized in Table 1.
Table 1. Summary of imaging guidance possibilities for bone biopsies in different skeletal sites according to lesion radiologic patterns.
1 CT = computed tomography.
Additionally, several studies have underlined the feasibility, safety and efficacy of MRI guidance for bone biopsies. The advantages of MR imaging guidance are several. MRI uses no ionizing radiation in contrast to fluoroscopy and CT, provides improved bone marrow and soft tissue assessment and has multiplanar capabilities. Additionally, some bone lesions may only be visible on MRI. Current routine applications of this tool in clinical settings are still limited, mainly because of the long acquisition time and high costs.
In a large series by Liu et al. including 67 MRI-guided spinal biopsies, safe and accurate diagnostic results were reported, but a relatively high procedural time from 27 to 56 min (mean 35 min) 
5. Clinical Indications
Nowadays, CT-guided skeletal biopsies are considered the suggested first line tool for histopathologic and/or microbiologic diagnoses of bone lesions. This tool is the method of choice for the evaluation of skeletal lesions suspected to be malignant, i.e., suspicious primary bone tumors or systemic cancer metastasis.
The indications for imaging-guided skeletal biopsy are several. One of the most common indications is confirming metastasis in a patient with a known primary malignancy (Figure 1).
Figure 1. A male patient with a recent diagnosis of prostate cancer was put forward for a CT-guided biopsy (right, square) of a calcified intramedullary lesion of the distal femur metaphysis with increased SUV at PET-CT (oval dotted lines). A diagnosis of enchondroma, already suspected by radiological reports, was confirmed by a biopsy, excluding metastasis.
Even if the radiological studies together with anamnestic data indicate a diagnosis of bone metastasis, a CT-guided biopsy is indicated not only for histopathologic confirmation. Indeed, by deepening metastatic bone lesion profiling, molecular and receptor characterization can be obtained, with relevant impacts on the patient management and treatment choice 
. Particularly, the hormone receptor status can be safely and accurately assessed on bone metastases with CT-guided samples, permitting the possibility of optimal treatments and a more personalized care 
Recurrence identification and tumor treatments response (e.g., % of necrosis obtained after therapy) are other well-known indications for bone biopsies 
. Moreover, a bone biopsy is indicated when an unexpected non-traumatic fracture occurs. Particularly, determining the nature of a non-traumatic vertebral collapse is a recognized indication for these procedures 
Investigating for infection (microbiological analyses) or the differential diagnosis between infections (particularly spondylodiscitis) and other bone lesions is another indication as well 
. Spondylodiscitis is usually diagnosed by a combination of clinical, laboratorial and imaging data. A percutaneous biopsy is usually recommended to isolate the pathogenic microorganisms in patients with negative blood cultures. Despite its low microbiologic yield, a CT-guided percutaneous biopsy is frequently preferred over an open biopsy due to its relative safety, low morbidity and inexpensive cost. Moreover, deep soft tissue infections, in selected cases and especially if bone involvement is present, may require a CT-guided biopsy.
It is important to know that in the case of primary bone sarcomas of the appendicular skeleton, a surgical incisional biopsy permits to obtain larger samples with the aim of deepening analyses for molecular and therapeutic investigations 
. Due to this, when a radiographic feature of primary bone sarcoma is clearly recognized, the patient could be submitted directly for an incisional surgical biopsy.
Nonetheless, CT-guided biopsies may be preferred to the standard ultrasound guidance for selected deep soft tissue neoplasms, especially if bone erosion is present 
In Figure 2, all the main clinical indications for a bone biopsy are summarized.
Figure 2. Summary of clinical indications for a bone biopsy.
6. Contraindications and Complications
The main contraindications are represented by coagulation disorders and anticoagulant treatments, increasing the risk of local bleeding/hematoma, and a decreased platelet count (<50,000/mm3
). The Society of Interventional Radiology recommends correction of an INR (international normalized ratio) to less than 1.5–1.8. If the platelet count is fewer than 50,000/mm3
, platelet transfusion may be necessary and anticoagulant and antiplatelet medications may be stopped depending on the unique pharmacologic properties of each drug 
Complications are reported to be very infrequent and usually mild. The main complications are transient paresis (due to the anesthetic effect on nerves) (0.09%) and hematoma (0.002%) 
. Transient and minor complications such as vasovagal syncope are commonly observed, especially in the supine position rather than the prone position.
Pain during the procedure is a relevant concern, since bone lesions and the biopsy itself may be extremely painful in some cases. Local anesthetic, deep/mild sedation or general anesthesia and neural blocks should be carefully planned according to the lesion type and location and the patient’s age.