MRI-based vertebral bone quality score: relationship with age and reproducibility.

Vertebral bone quality (VBQ) score is an opportunistic measure of bone mineral density using routine preoperative MRI in spine surgery. VBQ score positively correlates with age and is reproducible across serial scans. However, extrinsic factors, including MRI machine and protocol, affect the VBQ score and must be standardized. PURPOSE: The purposes of this study were to determine whether VBQ score increased with age and whether VBQ remained consistent across serial MRI studies obtained within 3 months. METHODS: This retrospective study evaluated 136 patients, age 20-69, who received two T1-weighted lumbar MRI within 3 months of each other between January 2011 and December 2021. VBQ(L1-4) score was calculated as the quotient of L1-L4 signal intensity (SI) and L3 cerebral spinal fluid (CSF) SI. VBQ(L1) score was calculated as the quotient of L1 SI and L1 CSF SI. Regression analysis was performed to determine correlation of VBQ(L1-4) score with age. Coefficient of variation (CV) was used to determine reproducibility between VBQ(L1-4) scores from serial MRI scans. RESULTS: One hundred thirty-six patients (mean ± SD age 44.9 ± 12.5 years; 53.7% female) were included in this study. Extrinsic factors affecting the VBQ score included patient age, MRI relaxation time, and specific MRI machine. When controlling for MRI relaxation/echo time, the VBQ(L1-4) score was positively correlated with age and had excellent reproducibility in serial MRI with CV of 0.169. There was excellent agreement (ICC > 0.9) of VBQ scores derived from the two formulas, VBQ(L1) and VBQ(L1-4). CONCLUSION: Extrinsic factors, including MRI technical factors and age, can impact the VBQ(L1-4) score and must be considered when using this tool to estimate bone mineral density (BMD). VBQ(L1-4) score was positively correlated with age. Reproducibility of the VBQ(L1-4) score across serial MRI is excellent especially when controlling for technical factors, supporting use of the VBQ score in estimating BMD. The VBQ(L1) score was a reliable alternative to the VBQ(L1-4) score.

Preoperative bone health assessment and optimization in spine surgery.

OBJECTIVE: The purpose of this investigation was to characterize the bone health in preoperative spine surgery patients. This information will provide a framework to understand the needs and methods for providing bone health optimization in elective spine surgery patients. METHODS: A retrospective study of 104 patients undergoing bone health optimization was performed. Patients were selected based on risk factors identified by the surgeon and suspected compromised bone health. Evaluation included history and examination, laboratory investigations, and bone mineral density (BMD) at 3 sites (femoral neck, lumbar spine, and radius). Patients' bone status was classified using WHO criteria and expanded criteria recommended by the National Osteoporosis Foundation (NOF). The 10-year Fracture Risk Assessment Tool (FRAX) scores of the hip and major osteoporotic fracture (MOF) were calculated with and without femoral neck BMD, with spine BMD, and with the trabecular bone score (TBS). Antiresorptive and anabolic agents were provided in accordance with meeting NOF criteria for treatment of osteoporosis. RESULTS: The mean patient age was 69.0 years, and 81% of patients were female. The mean historical height loss was 5.6 cm, and 54% of patients had a history of fracture. Secondary osteoporosis due to chronic renal failure, inflammatory arthritis, diabetes, and steroid use was common (51%). The mean 25-hydroxy vitamin D was 42.4 ng/ml and was normal in 81% of patients, with only 4 patients being deficient. The mean T-scores were -2.09 (SD 0.71) of the femoral neck, -0.54 (1.71) of the lumbar spine, and -1.65 (1.38) of the distal radius. These were significantly different. The 10-year FRAX MOF score was 20.7%, and that for hip fracture was 6.9% using the femoral neck BMD and was not significantly different without the use of BMD. The FRAX risk-adjusted score using the lumbar spine BMD and TBS was significantly lower than that for the hip. Osteoporosis was present in 32.1% according to WHO criteria compared with 81.6% according to NOF criteria. Antiresorptive medications were recommended in 31 patients and anabolic medications in 44 patients. CONCLUSIONS: Surgeons can reliably identify patients with poor bone health by using simple criteria, including historical height loss, history of fracture, comorbidities associated with osteoporosis, analysis of available imaging, and calculation of FRAX score without BMD. High-risk patients should have BMD testing and bone health assessment. In patients with osteoporosis, a comprehensive preoperative bone health assessment is recommended and, if warranted, pharmacological treatment should be started.

Osteoporosis in spine surgery patients: what is the best way to diagnose osteoporosis in this population?

OBJECTIVE: The goal of this study was to compare different recognized definitions of osteoporosis in patients with degenerative lumbar spine pathology undergoing elective spinal fusion surgery to determine which patient population should be considered for preoperative optimization. METHODS: A retrospective review of patients in whom lumbar spine surgery was planned at 2 academic medical centers was performed, and the rate of osteoporosis was compared based on different recognized definitions. Assessments were made based on dual-energy x-ray absorptiometry (DXA), CT Hounsfield units (HU), trabecular bone score (TBS), and fracture risk assessment tool (FRAX). The rate of osteoporosis was compared based on different definitions: 1) the WHO definition (T-score ≤ -2.5) at total hip or spine; 2) CT HU of < 110; 3) National Bone Health Alliance (NBHA) guidelines; and 4) "expanded spine" criteria, which includes patients meeting NBHA criteria and/or HU < 110, and/or "degraded" TBS in the setting of an osteopenic T-score. Inclusion criteria were adult patients with a DXA scan of the total hip and/or spine performed within 1 year and a lumbar spine CT scan within 6 months of the physician visit. RESULTS: Two hundred forty-four patients were included. The mean age was 68.3 years, with 70.5% female, 96.7% Caucasian, and the mean BMI was 28.8. Fracture history was reported in 53.8% of patients. The proportion of patients identified with osteoporosis on DXA, HUs, NBHA guidelines, and the authors' proposed "expanded spine" criteria was 25.4%, 36.5%, 75%, and 81.9%, respectively. Of the patients not identified with osteoporosis on DXA, 31.3% had osteoporosis based on HU, 55.1% had osteoporosis with NBHA, and 70.4% had osteoporosis with expanded spine criteria (p < 0.05), with poor correlations among the different assessment tools. CONCLUSIONS: Limitations in the use of DXA T-scores alone to diagnose osteoporosis in patients with lumbar spondylosis has prompted interest in additional methods of evaluating bone health in the spine, such as CT HU, TBS, and FRAX, to inform guidelines that aim to reduce fracture risk. However, no current osteoporosis assessment was developed with a focus on improving outcomes in spinal surgery. Therefore, the authors propose an expanded spine definition for osteoporosis to identify a more comprehensive cohort of patients with potential poor bone health who could be considered for preoperative optimization, although further study is needed to validate these results in terms of clinical outcomes.

Fracture in Patients with Normal Bone Mineral Density: An Evaluation of the American Orthopaedic Association's Own the Bone Registry.

BACKGROUND: Fractures often occur in patients with normal dual x-ray absorptiometry (DXA)-measured bone mineral density (BMD). DXA does not consider clinical fracture risk factors or bone quality. We hypothesized that patients with normal BMD who sustain a fracture have other characteristics suggesting abnormal bone and an elevated fracture risk requiring additional bone health evaluation and potential anti-osteoporotic treatment. METHODS: A total of 7,219 patients who were ≥50 years of age, had sustained a fracture from July 2016 to July 2021, and had DXA data in the American Orthopaedic Association's Own the Bone (AOA OTB) registry were included in this study. The index and prior fracture site data were obtained. BMD status was classified by the World Health Organization T-score criteria. The Fracture Risk Assessment Tool (FRAX) scores with and without BMD were calculated in patients with normal BMD. An elevated risk was defined as a major osteoporotic fracture risk of ≥20% or a hip fracture risk of ≥3%. RESULTS: The mean patient age (and standard deviation) was 70.8 ± 9.71 years, 84% of patients were female, and 92% of patients were Caucasian. Normal BMD was present in 8.6% of patients. The index fracture was a major osteoporotic fracture in 68.6% of patients with normal BMD and 75.6% of patients with osteoporosis. The most common site for index and prior fractures other than major osteoporotic fractures was the foot and ankle; of patients with normal BMD, 13.9% had this as the most common index site and 17.4% had this as the most common prior site. The FRAX risk calculated without BMD was elevated in 72.9% of patients with normal BMD, and the FRAX risk calculated with BMD was elevated in 12.0% of patients. CONCLUSIONS: Most patients with a fracture and normal BMD met indications, including a prior fracture or elevated FRAX risk, for anti-osteoporotic therapies. Most patients were Caucasian and therefore potentially had a higher baseline fracture risk. The FRAX risk calculated without BMD was elevated more often than the FRAX risk with BMD, implying that clinical risk factors, which highlight multiple opportunities for non-pharmacologic secondary fracture prevention, should be considered along with DXA. Fractures other than major osteoporotic fractures were more common in patients with normal BMD, suggesting that minor fractures in adults who are ≥50 years of age should be considered sentinel events warranting further evaluation. Surgeons must recognize that other important risk factors apart from BMD may help to guide further bone health evaluation. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Clinical risk factor status in patients with vertebral fracture but normal bone mineral density.

BACKGROUND CONTEXT: Normal bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DXA) is present in approximately 10% of older adults with fracture. BMD alone does not evaluate bone quality or clinical risk factors, and therefore, may not adequately capture a patient's fracture risk. Thus, despite a normal DXA-measured BMD, the underlying bone may be abnormal, suggesting that further bone health evaluation, and potentially, pharmacologic treatment may be warranted. PURPOSE: To determine the prevalence of normal BMD, clinical fracture risk factors, and quantitative risk of fracture using the Fracture Risk Assessment Tool (FRAX) in vertebral fracture patients with normal BMD enrolled in the Own the Bone registry, thus facilitating identification of those who meet criteria for anti-osteoporosis therapy. STUDY DESIGN/SETTING: Retrospective, national registry-based cohort. PATIENT SAMPLE: From July 2016 to July 2021, 1,807 patients age ≥50 who sustained a vertebral fracture and had DXA data available from within 2 years prior to enrollment in the American Orthopaedic Association's Own the Bone (AOA OTB) registry were included. OUTCOME MEASURES: World Health Organization (WHO) DXA T-score based bone classification criteria; FRAX risk scores of major osteoporotic fracture or hip fracture. METHODS: Demographic data, prior fracture site, and clinical fracture risk factors were collected. BMD status was classified by the WHO T-score criteria: ≥ -1.0 normal, -1.1 to -2.4 osteopenia, and ≤ -2.5 osteoporosis, with low bone mass including either osteopenia or osteoporosis. In normal BMD patients, FRAX scores were calculated with and without BMD, with the treatment threshold defined as a major osteoporotic fracture risk ≥20% or hip fracture risk ≥3%. RESULTS: Mean±SD age was 72.0±9.7, 78.1% were female, and 92.4% were Caucasian. Normal BMD was present in 7.9%. Clinical fracture risk factors including alcohol use ≥3 units/day and history of ≥2 falls in the year prior to enrollment were more common in normal BMD (11.2% and 28%, respectively) compared to low bone mass patients (3.4% and 25.2%, respectively). A prior vertebral fracture had occurred in 49.5% with normal BMD compared to 45.8% with low bone mass, while a prior non-major osteoporotic fracture occurred in 28.9% and 29.3% of normal BMD and low bone mass patients, respectively. In normal BMD patients, either a prior fracture or FRAX risk with BMD meeting treatment thresholds was present in 85%. CONCLUSIONS: Clear indications for receipt of pharmacologic therapy, ie, prior fracture or elevated fracture risk, were present in most patients with vertebral fracture and normal BMD enrolled in the AOA OTB. Prior non-major osteoporotic fractures were common and may be useful indicators of underlying bone disease. Surgeons must recognize that other important risk factors apart from BMD may indicate poor bone health, and thus, help guide further bone health evaluation.

Bone Health Optimization in Orthopaedic Surgery.

BACKGROUND: Osteoporosis is associated with adverse orthopaedic surgical outcomes. Bone health optimization is a preoperative intervention intended to reduce the likelihood of postoperative complications. We aimed to characterize a patient cohort referred for bone health optimization to test the hypothesis that poor bone quality is common in orthopaedic surgery and that many such patients meet guidelines for osteoporosis treatment. METHODS: This retrospective study evaluated 124 patients referred for bone health optimization who were ≥50 years of age and candidates for arthroplasty or thoracolumbar surgery. The Fracture Risk Assessment Tool (FRAX) risk factors and dual x-ray absorptiometry (DXA) results were collected. When available, opportunistic computed tomographic (CT) imaging and the trabecular bone score were evaluated. The World Health Organization (WHO) diagnostic and National Osteoporosis Foundation (NOF) treatment guidelines were applied. RESULTS: All patients were referred by their orthopaedic surgeon; their mean age was 69.2 years, 83% of patients were female, 97% were Caucasian, and 56% had sustained a previous fracture. The mean historical height loss (and standard deviation) was 5.3 ± 3.3 cm for women and 6.0 ± 3.6 cm for men. The mean lowest T-score of the hip, spine, or wrist was -2.43 ± 0.90 points in women and -2.04 ± 0.81 points in men (p < 0.08). Osteoporosis (T-score of ≤-2.5 points) was present in 45% of women and 20% of men; only 3% of women and 10% of men had normal bone mineral density. Opportunistic CT scans identified 60% of patients as likely having osteoporosis. The trabecular bone score identified 34% of patients with degraded bone microarchitecture and 30% of patients with partially degraded bone microarchitecture. The NOF threshold for osteoporosis treatment was met in 91% of patients. Treatment was prescribed in 75% of patients (45% anabolic therapy and 30% antiresorptive therapy). CONCLUSIONS: Osteoporosis, degraded bone microarchitecture, prior fracture, and elevated fracture risk were common. Given the high prevalence of impaired bone health in this cohort, we believe that bone health screening, including FRAX assessment, should be considered in selected patients undergoing orthopaedic surgery as part of the preoperative optimization for all adults who are ≥50 years of age. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Current approaches in regenerative medicine for the treatment of diabetes: introducing CRISPR/CAS9 technology and the case for non-embryonic stem cell therapy.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which the body destroys its pancreatic ß cells. Since these cells are responsible for insulin production, dysfunction or destruction of these cells necessitates blood glucose control through exogenous insulin shots. Curative treatment involves pancreas transplantation, but due to the incidence of transplant rejection and complications associated with immunosuppression, alternatives are being explored. Despite facing clinical challenges and issues with public perception, the field of regenerative stem cell therapy shows great promise for the treatment of diabetes. The idea of harnessing pluripotency to derive cells and tissues with characteristics of choice is astounding but feasible, and this review seeks to determine which method of stem cell derivation is preferable for diabetes treatment. In this report, we outline the methods for deriving human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and adult stem cells or progenitor cells to generate functional islet cells and related tissues. We discuss the specific uses and advantages of each method, and we comment on the ethics and public perceptions surrounding these methods and how they may affect the future of stem cell research. For the reasons outlined in this paper, we believe that non-embryonic stem cell lines, including iPSCs, somatic cell nuclear transfer lines, and adult tissue derived stem cells, offer the highest therapeutic potential for treating diabetes.