Bisphosphonate-loaded bone cement: Background, clinical indications and future perspectives.

Bisphosphonates represent an established treatment against bone resorption and osseous loss. Local application could help increase bone mineral density while minimizing their systemic use side-effects. Bone cement, used on a large scale in orthopedic surgery and a historically successful drug carrier, could represent an effective scaffold. The aim of this review was to investigate the alterations produced on the cement's structure and properties by this mixture, as well as its antiosteoporotic and antitumor effect. After a thorough research of articles, title screening and duplicate removal we retained 51 papers. Two independent authors performed abstract and full-text reading, finally leaving 35 articles included in this review. In the current literature, acrylic and calcium phosphate bone cement have been used as carriers. A combination with nitrogen-containing bisphosphonates, e.g., zoledronic acid, provokes modifications in terms of setting time prolongation and mechanical strength decline within acceptable levels, on the condition that the drug's quantity stays beneath a certain plateau. Bisphosphonates in bone cement seem to have a powerful anti-osteoclastic and osteogenic local impact as well as a direct cytotoxic effect against several neoplastic lesions. Further investigation on the subject is required, with specifically designed studies focusing on this method's advantages and potential clinical applications.

Atypical vertebral hemangioma: an aggressive form of a benign disease. Case Report and Literature Review.

Vertebral hemangiomas are an incidental and relatively common radiological finding and a benign tumor of vascular origin. VH are the most common spine tumors with an estimated incidence of 1.9-27% in the general population. Rarely, vertebral hemangiomas can exhibit extraosseous expansion with resulting compression of the spinal cord. Such lesions are termed aggressive or atypical vertebral hemangiomas (AVH) and account for less than 1% of spinal hemangiomas. A 68-year-old female was referred with progressive walking difficulty and sensory disturbances in her lower extremities. MRI imaging of the thoracic spine revealed a T1- and T2-weighted hyperintense lesion involving the T10 vertebra. Additionally, there was extraosseous extension of the tumor into the spinal canal, located both anterior and posterior to the spinal cord, causing severe spinal cord compression. A combined endovascular and surgical approach (arterial coil embolization and en bloc resection) for treatment was decided. Although vertebral hemangiomas are an incidental and relatively common radiological finding, the findings of our case were consistent with an aggressive hemangioma with atypical MRI and clinical prognostic characteristics. In summary, the present case highlights the need for multidisciplinary approach and in-depth knowledge of this rare pathologic entity.

Association of vitamin D, BMD and knee osteoarthritis in postmenopausal women.

OBJECTIVES: The aim of this study was to analyze the association of knee OA with bone mineral density (BMD) and vitamin D serum levels in postmenopausal women. METHODS: A cross-sectional study including 240 postmenopausal women with knee OA was conducted. Demographic data were recorded along with balance and functionality scores. Knee OA severity was assessed by the radiological Kellgren & Lawrence scale. BMD and T-scores were calculated in hips and lumbar spine. Serum levels of vitamin D were also measured. RESULTS: High BMI (p<0.005), high number of children (p=0.022) and family history of hip fracture (p=0.011) are significantly associated with knee OA severity. Lumbar spine OP is negatively associated with knee OA (p<0.005). A significant difference was detected between vitamin D deficiency and severe knee OA, adjusted for BMD [OR (95%CI); 3.1 (1.6-6.1), p=0.001]. BMD does not affect the relationship of vitamin D levels in relation to OA and vitamin D levels do not affect the relationship of BMD with OA. CONCLUSIONS: Low BMD has a protective role against knee OA while vitamin D deficiency contributes significantly to knee OA severity. However, the association between OA and OP is not affected by vitamin D deficiency and the association of OA and vitamin D serum levels is not affected by BMD.

Diagnosis, Pathophysiology and Management of Hypercalcemia in Malignancy: A Review of the Literature.

Hypercalcemia of malignancy is the most common life-threatening metabolic disorder in patients with advanced stage cancers and is a sign of poor prognosis. It usually presents with markedly elevated calcium level and is severely symptomatic. It is associated with hematological malignancies, such as multiple myeloma, non-Hodgkin lymphoma, leukemias and solid cancers, particularly renal and breast carcinomas as well as squamous cell carcinomas of any organ. Several mechanisms have been implicated in the development of hypercalcemia of malignancy amongst them the osteolytic related hypercalcemia, parathyroid hormone-related peptide (PTHrP) mediated hypercalcemia, extrarenal 1,25 dixydroxyvitamin D (calcitriol) mediated hypercalcemia and parathyroid hormone (PTH) related hypercalcemia either ectopic in origin or in patients with parathyroid carcinoma. Clinical history and and physical examination could point towards the correct diagnosis confirmed by the above-mentioned biochemical mediators of hypercalcemia. Early diagnosis and treatment lowering calcium levels in the blood can improve symptoms and the quality of life of these patients and avoid delays for further antitumor therapy.

The Role of Bone Mineral Density in a Successful Lumbar Interbody Fusion: A Narrative Review.

BACKGROUND: The incidence of osteoporosis is a prime concern, especially in parts of the world where the population is aging, such as Europe or the US. Many new therapy strategies have been described to enhance bone healing. Lumbar interbody fusion (LIF) is a surgical procedure that aims to stabilize the lumbar spine by fusing two or more vertebrae using an interbody cage. LIF is a standard treatment for various spinal conditions, such as degenerative disc disease, spinal stenosis, and spondylolisthesis. However, successful fusion is challenging for patients with osteoporosis due to their reduced bone mineral density (BMD) and increased risk of cage subsidence, which can lead to implant failure and poor clinical outcomes. METHODS:  A comprehensive literature search yielded 220 articles, with 16 ultimately included. Keywords included BMD, cage subsidence, osteoporosis, teriparatide, and lumbar interbody fusion. RESULTS:  This review examines the relationship between BMD and LIF success, emphasizing the importance of adequate bone quality for successful fusion. Preoperative assessment methods for BMD and the impact of low BMD on fusion rates and patient outcomes are discussed. Additionally, techniques to improve fusion success in patients with weakened bone density, such as biological enhancement and BMD-matched interbody cages, are explored. However, consensus on the exact BMD threshold for a successful outcome remains elusive. CONCLUSION:  While an apparent correlation between BMD and fusion rate in LIF procedures is acknowledged, conclusive evidence regarding the precise BMD threshold indicative of an increased risk of unfavorable outcomes remains elusive. Surgeons are advised to exercise caution in surgical planning and follow-up for patients with lower BMD. Furthermore, future research initiatives, particularly longitudinal studies, are encouraged to prioritize the examination of BMD as a fundamental risk factor, addressing gaps in the literature.

White Cord Syndrome Following Cervical Surgery in a Patient With Klippel-Feil Syndrome: A Case Report.

White cord syndrome is a rare entity, as there are very few cases described in the current literature. Postoperative MRI examination reveals cord intrinsic changes, including edema and ischemia. It is also described as a reperfusion injury of the spinal cord. This report depicts a rare case of "white cord syndrome" with tetraplegia after posterior laminectomy and fusion of the cervical spine in a patient with Klippel-Feil syndrome. A 33-year-old male patient with Klippel-Feil syndrome presented to our department with cervical myelopathy, claudication, deteriorating neurological status, imbalance, and lower limb spasticity. Due to kyphotic malformation of the cervical spine, a two-stage surgical intervention was scheduled. The patient first underwent anterior spinal fusion of C4-C6 with corpectomy of C5, where many anatomical and visceral differentiations were signed, so the surgical team was enhanced by a vascular surgeon. The postoperative period was uneventful and the patient was discharged after a week of hospitalization without any neurological deterioration. A second surgical intervention was scheduled after two months where laminectomy of C5-C7 and posterior fusion of C5-T1 were carried out. However, due to intraoperative spinal instability and various anatomical spinal variations, a third surgery, which would be occipitocervical fusion, was decided as the final surgical solution. During the third surgical operation, after the laminectomy of C1 to C5 and the placement of the occipital plate, the screws, and the two rods in situ, complete nullification of the intraoperative neurophysiologic control was signed. The internal fixation was removed immediately, the wake-up test revealed tetraplegia below C5, and the patient was transferred to the ICU. Immediate MRI revealed no spinal cord hematoma; however, spinal cord edema was present. The patient underwent a tracheostomy and remained quadriplegic with a sensory level of T8 and motor level of C5 and was discharged to a rehabilitation center. The possibility of white cord syndrome should be explained by surgeons before any cervical decompression surgery, as well as a thorough neurological examination should be performed postoperatively. The early recognition and prompt management of white cord syndrome is recommended.

Impact of COVID-19 Pandemic on Fragility Fractures of the Hip: An Interrupted Time-Series Analysis of the Lockdown Periods in Western Greece and Review of the Literature.

Since December 2019, the COVID-19 pandemic has had a significant impact on healthcare systems worldwide, prompting policymakers to implement measures of isolation and eventually adopt strict national lockdowns, which affected mobility, healthcare-seeking behavior, and services, in an unprecedented manner. This study aimed to analyze the effects of these lockdowns on hip-fracture epidemiology and care services, compared to nonpandemic periods in previous years. We retrospectively collected data from electronic patient records of two major hospitals in Western Greece and included patients who suffered a fragility hip fracture and were admitted during the two 5-week lockdown periods in 2020, compared to time-matched patients from 2017-2019. The results showed a drop in hip-fracture incidence, which varied among hospitals and lockdown periods, and conflicting impacts on time to surgery, time to discharge after surgery, and total hospitalization time. The study also found that differences between the two differently organized units were exaggerated during the COVID-19 lockdown periods, highlighting the impact of compliance with social-distancing measures and the reallocation of resources on the quality of healthcare services. Further research is needed to fully understand the specific variations and patterns of geriatric hip-fracture care during emergency health crises characterized by limited resources and behavioral changes.

Distraction over nail using circular external fixation for septic pseudarthrosis of the tibia.

We present a report of nine patients (eight women and one man; mean age 37 years) from 2010 to 2012 with septic pseudarthrosis of the tibia treated with bone transport over an intramedullary nail using a circular external fixator. The mean follow-up was 15 months (range: 10-21 months). A two stage approach was used. At the first stage, removal of the primary osteosynthesis and extensive bone debridement to healthy, bleeding bone margins was performed. The bone defect was packed with antibiotic loaded cement beads, and stabilization of the tibia was done with a unilateral external fixator or with a long leg posterior splint. The mean size of bone defect was 4 cm (range: 3.5-5.5 cm). At the second stage, two consecutive negative wound cultures and normal values of blood cell count, C-reactive protein (CRP), and estimated sedimentation rate (ESR) were obtained. Then we reamed and locked the intramedullary nailing of the tibia, applied a circular external fixator, and performed percutaneous corticotomy of the tibia opposite the site of the bone defect. Bone distraction over the nail was initiated at the eighth postoperative day at a rate of 1 mm/day. At the last follow-up, union was achieved in all cases without recurrence of bone infection. All patients experienced excellent (n=3) or good (n=6) knee and ankle function, as well as complete return to their daily activities. Two patients experienced pin-tract infection, and one patient experienced anterior knee pain at the entry point of the nail.

Intramedullary Nailing of Concurrent Bilateral Tibial Stress Fractures Followed by Unilateral Tension Plating for a Nonunion in a Vitamin D-Deficient Elite Football Player.

Stress fractures consist of a type of bone fracture that occurs due to repetitive mechanical stress instead of acute forceful injuries that cause common fractures. They are quite common among athletes at all competition levels and in army recruits who are expected to undergo extremely demanding exercises. While stress fractures can occur in any long bone, they are usually associated with the most common weight-bearing sites of lower extremities such as phalanges, metatarsals, tarsal bones, the tibia, and fibula. In this study, we report the surgical management of a 23-year-old African football player who sustained concurrent bilateral anterior cortex tibial midshaft fractures. His initial symptom was persistent subacute pain in both tibias. The initial conservative treatment was not successful and the patient was surgically treated with bilateral tibial intramedullary nails. However, the right tibia subsequently developed nonunion. Both intramedullary nails were removed and a tension plate was applied with an autologous iliac crest graft on the right tibia. Further blood test analysis revealed a significant vitamin D deficiency. The purpose of this article is to report different outcomes of the same primary surgical treatment for concurrent bilateral tibia stress fracture syndrome in an elite athlete due to vitamin D deficiency. To our knowledge, this is the first study that highlights the necessity of revising one of the intramedullary nailed concurrent tibia stress fractures with a tension plate and autologous graft to treat the established nonunion in an elite football player.

Off-Label Use of Teriparatide in Spine.

Teriparatide belongs to osteo-anabolic compounds and has been used in recent years to treat patients with osteoporosis, with the benefits of increased bone density. Its osteo-anabolic action has led to the investigation of the use of teriparatide for the improvement of bone quality. Apart from the enhancement of fracture union, teriparatide has been extensively studied in the promotion of fusion rate after spinal fusion. This study summarizes the preclinical and clinical results of the off-label use of teriparatide in the spine, and specifically its intermittent administration after instrumented spinal arthrodesis along with its impact on the spinal bone quality and spinal bone mineral density.

Inhibition versus activation of canonical Wnt-signaling, to promote chondrogenic differentiation of Mesenchymal Stem Cells. A review.

Canonical Wnt signaling regulation is essential for controlling stemness and differentiation of mesenchymal stem cells (MSCs). However, the mechanism through which canonical Wnt-dependent MSC lineage commitment leads to chondrogenesis is controversial. Some studies hypothesize that inhibition of canonical Wnt signaling induces MSC chondrogenic differentiation, while others support that the pathway should be activated to achieve MSC chondrogenesis. The purpose of the present review is to analyze data from recent studies to elucidate parameters regarding the role of canonical Wnt signaling in MSC chondrogenic differentiation.

Fractures After Removal of Spinal Instrumentation: Revisiting the Stress-Shielding Effect of Instrumentation in Spine Fusion.

BACKGROUND: Many practicing spine surgeons believe that instrumentation can be removed during revision surgery in successful posterolateral or anterior spinal fusions, confirmed by computed tomography and intraoperative exploration. The stress-shielding effect of spinal instrumentation was well described in the late 1980s and 1990s but has not received recent attention. Despite the paucity of recent literature, concepts underlying the biology and biomechanics of the spinal fusion mass remain particularly salient given the increasing incidence of revision spinal fusion surgery. The aim of this study was to highlight a potential complication of instrumentation removal owing to stress shielding of instrumentation on the spinal column and fusion mass. METHODS: A retrospective review was performed, and a small case series was described. RESULTS: In 3 cases, despite apparent solid fusion demonstrated on preoperative computed tomography and confirmed by intraoperative exploration, new fractures developed after removal of instrumentation. In these cases, fracture occurred at the transition zone between the newly rigid instrumented area and previous fusion. This highlights the relative weakness of the fusion and may be explained by the stress-shielding effect of instrumentation within the fusion mass. CONCLUSIONS: Spinal instrumentation revision requires careful consideration, and routine implant removal should not be performed. The presence of a solid fusion on computed tomography and/or at intraoperative exploration may not justify implant removal in these cases. In cases of extension of a fusion, use of a bridging connection to the new implants should be considered. The cases presented demonstrate the consequences of the stress-shielding effect of implants on the spine and fusion mass.

Smoking is a significant determinant of low serum vitamin D in young and middle-aged healthy males.

OBJECTIVE: We aimed to determine the prevalence of 25(OH)D (D2 and D3 independently) inadequacy in healthy young/middle-aged men and to investigate its relationship with BMD, bone markers, demographic and lifestyle parameters such as age, BMI, smoking, alcohol consumption and dietary calcium intake. DESIGN: We determined 25(OH)D levels using LC-MS/MS, a robust method for measurement of both 25(OH)D3 and 25(OH)D2, iPTH, osteocalcin, beta C terminal cross-linked telopeptides of type I collagen (b-CTXs), procollagen type 1 amino-terminal propeptide (PINP), BMD at L2-L4 and proximal femur, smoking habits, daily dietary calcium intake and alcohol consumption in 181 randomly selected healthy men aged 20-50y. RESULTS: The prevalence of vitamin D deficiency (25(OH)D < 20 ng/ml) was 50.3%. Only 8.8% of the participants had vitamin D sufficiency (25(OH)D ≥ 30 ng/ml). We found a strong correlation between 25(OH)D and smoking in the totality of participants (p<0.001). 25(OH)D level was lower by approximately 4.3 ng/dl (p<0.001) in a smoker compared to a non-smoker among the totality of participants, while this value increased to 9.2 ng/ml in the 40-50y subgroup (p=0.003). A multinomial logistic regression model demonstrated that a young smoker (20-29y) had 58% increased likelihood of having vitamin D deficiency compared to a non-smoker of the same age group (p=0.041). CONCLUSIONS: A high prevalence of vitamin D deficiency was identified in a young and middle-aged male population. Smoking is a significant determinant of serum 25(OH)D, while it increases significantly the likelihood of having vitamin D deficiency. In our hands, vitamin D levels are not a determinant of bone turnover and BMD in this population.

Hypovitaminosis D as a risk factor of subsequent vertebral fractures after kyphoplasty.

BACKGROUND CONTEXT: Over the past 20 years, methods of minimally invasive surgery have been developed for the treatment of vertebral compression fractures. Balloon kyphoplasty and vertebroplasty are associated with a recurrent fracture risk in the adjacent levels after the surgical procedure. In certain patient categories with impaired bone metabolism, the risk of subsequent fractures after kyphoplasty is increased. PURPOSE: To determine the incidence of recurrent fractures after kyphoplasty and explore whether the status of bone metabolism and 25-hydroxyvitamin D (25(OH)D) levels affect the occurrence of these fractures. STUDY DESIGN: Prospective longitudinal clinical study. PATIENT SAMPLE: Forty female postmenopausal women with primary osteoporosis and acute symptomatic vertebral compression fractures. OUTCOME MEASURES: Identification of new vertebral fractures and documentation of indicators of bone metabolism. METHODS: A total of ninety-eight kyphoplasties were performed in 40 female patients. Balloon kyphoplasty was performed on all symptomatic acute vertebral compression fractures. Age, body mass index, history of tobacco use, number of initial vertebral fractures, intradiscal cement leakage, history of nonspinal fractures, use of antiosteoporotic medications, bone mineral density, bone turnover markers, and 25(OH)D levels were assessed. All participants were evaluated clinically and/or radiographically. Follow-up period was 18 months. RESULTS: The mean population age was 70.6 years (range, 40-83 years). After initial kyphoplasty procedure, nine patients (11 levels) (22.5% of patients; 11.2% of levels) developed a postkyphoplasty vertebral compression fracture. Cement leakage was identified in seven patients (17.5%). The patients without recurrent fractures after kyphoplasty demonstrated higher levels of 25(OH)D (22.6±5.51 vs. 14.39±7.47; p=.001) and lower N-terminal cross-linked telopeptide values (17.11±10.20 vs. 12.90±4.05; p=.067) compared with the patients with recurrent fractures. CONCLUSIONS: Bone metabolism and 25(OH)D levels seem to play a role in the occurrence of postkyphoplasty recurrent vertebral compression fractures.

Bone anabolic versus bone anticatabolic treatment of postmenopausal osteoporosis.

Increased bone fragility after menopause is commonly associated with accelerated bone loss and aggressive osteoclastic function. This is attributed to increased RANKL production and impaired osteoprotegerin synthesis. Fast bone loss leads to trabecular perforations, dramatic diminution of bone strength, and unexpected fractures. To avoid osteoporotic fractures, elimination of fast bone loss is recommended. Antiosteoclastic drugs, apart from estrogens, are the selective estrogen receptor modulators, calcitonins, and amino-bisphosphonates. These drugs increase bone mass by 1-5%, but reduce the relative risk of a vertebral fracture by 30-70%. Long-term exposure to bisphosphonates may be related to low bone turnover. In elderly and severe osteoporosis, antiosteoclastic regimens hardly correct the depressed osteoblastic function. Intermittent teriperatide stimulates osteoblastic function, improves bone geometry, and has an additional analgesic effect. While both anticatabolic and anabolic agents increase bone mass and decrease the risk of spinal fractures and occasionally of the fracture of the femoral neck, there are differences in the mode of their action. These pathophysiological differences are tentative therapeutic tools for the prevention of osteoporotic fractures. A fast bone loss, associated with increased biochemical markers, is the main indicator for anticatabolic agents, while impaired bone geometry, normal or low bone markers, and established bone architectural changes are in favor of the anabolic agents. Strontium ranelate combines the anticatabolic effect with an additional anabolic action.

Acute cholangitis due to pancreatic metastasis from squamous cell lung carcinoma: a case report and review of literature.

INTRODUCTION: The pancreas is a well-documented but relatively uncommon site of non-small-cell cancer metastases. However, at the time of diagnosis the disease is usually locoregionally advanced, therefore therapeutic management is mostly palliative and symptomatic. CASE PRESENTATION: We report the case of a 77-year-old Caucasian male patient who presented initially with a clinical picture of acute cholangitis approximately 2 years after a left lower lobectomy for a low-grade squamous lung carcinoma. CT scan imaging of the abdomen and chest revealed an abnormal growth of the pancreatic head and distention of both the intra- and extra-hepatic billiary tree, whereas osteolytic abnormalities were observed of the 5th left rib, consistent with secondary deposits. Initially an endoscopic retrograde cholangio-pancreatography (ERCP) and sphincterectomy was performed and a plastic stent was placed in the common bile duct to decompress the biliary tree. Cytological examination of the aspirate collected by FNA of the pancreatic lession under EUS guidance revealed cells consistent with a low grade squamous lung carcinoma. Two months later an open cholecystectomy along with a gastrojejunostomy was performed to relieve the patient's gastric outlet obstruction symptoms. Following remission of the patient's attack of acute cholangitis and excessive vomiting he was released from the hospital and instructed to initiate chemotherapy with vinorelbine. The patient succumbed to disseminated disease almost 5 months later. CONCLUSION: Symptomatic metastatic lesions of the pancreas from squamous cell carcinoma of the lung are infrequent. Typically, the patients remain asymptomatic until their disease reaches a fairly advanced stage and therapeutic options are limited to palliative measures. A high index of suspicion is the only way of early detection and potentially effective treatment for this rare localization of metastatic squamous lung carcinoma.