Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic.

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.

Reprint of: Thoracolumbar burst fractures associated with incomplete neurological deficit in patients under the age of 40: Is the posterior approach enough? Surgical treatment and results in a case series of 10 patients with a minimum follow-up of 2 years.

INTRODUCTION: Surgical management of thoracolumbar burst fractures is controversial. While the goals of surgical treatment are well accepted (i.e., fracture reduction and stabilization, neural elements decompression, and segmental angular deformity correction), the choice of the best surgical approach (i.e., posterior vs. anterior vs. combined approach) remains controversial. Several studies have debated the advantages of each surgical approach but there is no definitive evidence available to date, particularly in young adult patients. The aim of this study was to assess whether posterior approach alone can be a valid surgical treatment for patient under the age of 40 affected by thoracolumbar burst fractures and incomplete neurological deficits. MATERIAL AND METHODS: A total of 10 consecutive patients affected by thoracolumbar burst fractures associated with incomplete neurological deficits treated at our institution from January 2015 to February 2017 were included in our study. All patients were under the age of 40 at the time of injury and underwent decompression and stabilization using the posterior surgical approach alone. Demographics, clinical, and radiographic parameters were recorded preoperatively, postoperatively and at the latest available follow-up. The minimum follow-up was set at 2 years post-operatively. RESULTS: The mean operative time was 303.6 min (range, 138-486). Average blood loss was 756 mL (range, 440-2100). Nine out of ten patients returned to a normal neurological status after surgery while 1 patient showed some improvement but did not recover completely. Segmental kyphotic deformity improved from a mean of 21.8° before surgery to 14.8° at the time of the last follow-up. The anterior and posterior wall height of the fractured vertebra was restored with an average of 4 mm. The Visual Analogue Scale score reported an improvement from the mean preoperative value of 7.92 to 1.24 at the last follow-up; 8 out of 10 patients resumed physical activity while all of them returned to work. CONCLUSIONS: A single posterior surgical approach is an acceptable option in terms of clinical, radiological and functional outcomes at 2 years follow-up in patients under the age of 40 presenting with a thoracolumbar burst fracture and neurological deficit.

Thoracolumbar burst fractures associated with incomplete neurological deficit in patients under the age of 40: Is the posterior approach enough? Surgical treatment and results in a case series of 10 patients with a minimum follow-up of 2 years.

INTRODUCTION: Surgical management of thoracolumbar burst fractures is controversial. While the goals of surgical treatment are well accepted (i.e., fracture reduction and stabilization, neural elements decompression, and segmental angular deformity correction), the choice of the best surgical approach (i.e., posterior vs. anterior vs. combined approach) remains controversial. Several studies have debated the advantages of each surgical approach but there is no definitive evidence available to date, particularly in young adult patients. The aim of this study was to assess whether posterior approach alone can be a valid surgical treatment for patient under the age of 40 affected by thoracolumbar burst fractures and incomplete neurological deficits. MATERIAL AND METHODS: A total of 10 consecutive patients affected by thoracolumbar burst fractures associated with incomplete neurological deficits treated at our institution from January 2015 to February 2017 were included in our study. All patients were under the age of 40 at the time of injury and underwent decompression and stabilization using the posterior surgical approach alone. Demographics, clinical, and radiographic parameters were recorded preoperatively, postoperatively and at the latest available follow-up. The minimum follow-up was set at 2 years post-operatively. RESULTS: The mean operative time was 303.6 min (range, 138-486). Average blood loss was 756 mL (range, 440-2100). Nine out of ten patients returned to a normal neurological status after surgery while 1 patient showed some improvement but did not recover completely. Segmental kyphotic deformity improved from a mean of 21.8° before surgery to 14.8° at the time of the last follow-up. The anterior and posterior wall height of the fractured vertebra was restored with an average of 4 mm. The Visual Analogue Scale score reported an improvement from the mean preoperative value of 7.92 to 1.24 at the last follow-up; 8 out of 10 patients resumed physical activity while all of them returned to work. CONCLUSIONS: A single posterior surgical approach is an acceptable option in terms of clinical, radiological and functional outcomes at 2 years follow-up in patients under the age of 40 presenting with a thoracolumbar burst fracture and neurological deficit.

Pregnancy-associated osteoporosis (PAO) with multiple vertebral fragility fractures: diagnosis and treatment in a young primigravid woman.

PAO is an uncommon condition affecting pregnant women during last trimester or early post-delivery period; it is often asymptomatic or presents with pain related to some acute fragility fractures. The diagnosis is often delayed or missed, the etiology remains unknown and no guidelines about treatment have been published. We present one case of PAO in a 33-year-old primigravid woman presenting acute worsening back pain. Our patient was treated with a TLSO brace, oral 25 (OH)-vitamin D supplementation and Teriparatide for 6 months. A short review of the literature has been included and useful advice about how to suspect and diagnose this uncommon disease were given in order to recognize and treat such a debilitating and severe condition for young mothers as best as possible, based on the available scientific evidences.

Kyphoplasty vs conservative treatment: a case-control study in 110 post-menopausal women population. Is kyphoplasty better than conservative treatment?

OBJECTIVE: Osteoporosis is a highly prevalent disease worldwide. Consequences of vertebral osteoporotic fractures include pain and progressive vertebral collapse resulting in spinal kyphosis, decreased quality of life, disability and mortality. Minimally invasive procedures represent an advance to the treatment of osteoporotic VCFs. Despite encouraging results reported by many authors, surgical intervention in an osteoporotic spine is fraught with difficulties. Advanced patients age and comorbidities are of great concern. PATIENTS AND METHODS: We designed a retrospective case-control study on 110 post-menopausal women consecutively visited at our institution. Study population was split in a surgical and a conservative cohort, according to the provided treatment. RESULTS: Kyphoplasty treated patients had lower back pain VAS scores at 1 month as compared with conservatively treated patients (p < 0.05). EQ5D validated questionnaire also showed a better quality of life at 1 month for surgically treated patients (p < 0.05). SF-12 scores showed greater improvements at 1 month and 3 months with statistically significant difference between the two groups just at 3 months (p < 0.05). At 12 months, scores from all scales were not statistically different between the two cohorts, although surgically treated patients showed better trends than conservatively treated patients in pain and quality of life. Kyphoplasty was able to restore more than 54.55% of the original segmental kyphosis, whereas patients in conservative cohort lost 6.67% of the original segmental kyphosis on average. CONCLUSIONS: Kyphoplasty is a modern minimal invasive surgery, allowing faster recovery than bracing treatment. It can avoid the deformity in kyphosis due to VCF. In fact, the risk to develop a new vertebral fracture after the first one is very high.

Clinical predictors of vertebral osteoporotic fractures in post-menopausal women: a cross-sectional analysis.

BACKGROUND: Osteoporosis is a very common bone disorder and accounts for 1.4 million vertebral compression fractures (VCFs) per year, mostly in post-menopausal women. AIM: The aim of this study was to develop a risk scoring system to identify and gauge the risk of osteoporotic VCFs in post-menopausal women. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study on 477 post-menopausal women consecutively visited at our institution. We studied 15 different clinical variables, i.e. age, body mass index (BMI), weight, L1-L4 lumbar T-Score, L1-L4 lumbar Z-Score, L1-L4 lumbar bone mineral density (BMD), femoral neck T-Score, femoral neck Z-Score, femoral neck BMD, smoking habit, alcohol consumption, 25-OH-vitamin D, total alkaline phosphatase, bone alkaline phosphatase, and L4 vertebral volume. Study population was split in a derivation and a validation cohort. A logistic regression model was used to develop a predictive score of osteoporotic VCFs in the derivation cohort, finally the performance of the score was tested in the validation cohort. RESULTS: Age, L1-L4 lumbar T-Score, femoral neck T-Score, L4 vertebral volume, and smoking habit were found to be predictors of VCFs. To each variable a score from 0 to +12 was assigned to the magnitude of regression coefficient. A score ≥ 22 identified VCFs with a sensitivity of 87%/89% and a specificity of 87%/90% in the derivation and validation cohorts, respectively. CONCLUSIONS: Our findings indicate that a simple score derived from clinical history and routine diagnostic workout can be usefully employed to gauge the risk of fragility VCFs in post-menopausal women.

Epidemiological and clinical features of pyogenic spondylodiscitis.

Pyogenic spondylodiscitis (PS) is an uncommon but important infection, that represents 3-5% of all cases of osteomyelitis. The annual incidence in Europe has been estimated to be from 0.4 to 2.4/100,000. A has been reported, with peaks at age less than 20 years and in the group aged 50-70 years. The incidence of PS seems to be increasing in the last years as a result of the higher life expectancy of older patients with chronic debilitating diseases, the rise in the prevalence of immunosuppressed patients, intravenous drug abuse, and the increase in spinal instrumentation and surgery. PS is in most cases a hematogenous infection. Staphylococcus aureus is the most frequent causative microorganism, accounting for about one half of the cases of PS. Gram-negative rods are causative agents in 7-33% of PS cases. Coagulase-negative staphylococci (CoNS) have been reported in 5-16% of cases. Staphylococcus epidermidis is often related to post-operative infections and intracardiac device-related bacteremia. Unremitting back pain, characteristically worsening during the night, is the most common presenting symptom, followed by fever that is present in about one half of the cases. The mortality of PS ranges from 0 to 11%. In a significant number of cases, recrudescence, residual neurological defects or persistent pain may occur.

Post-operative spondylodiscitis.

Postoperative spine infections (PSIs) are a frequent and dreaded complication of spine surgery. Although different studies have been published, the prevalence of PSIs is thought to be about 5% for most spine surgical procedures. Different risk factors have been identified for PSIs. Among the others, extensive soft tissue dissection, longer operative time, soft tissue devitalization, and use of surgical instrumentation have been associated with higher risks of infection. Direct inoculation during surgery is the common infection route for PSIs. Gram-positive cocci (such as Staphylococcus aureus, Staphylococcus epidermidis and beta-hemolytic streptococci) are the most common pathogens. Gram-negative bacteria also play a role in PSIs and may be associated with systemic illness and multisystem organ failure. A high level of suspicion is of paramount importance in early diagnosis of PSIs. Clinical symptoms of PSIs may be subtle and the infection may become apparent only in its late stages. Early diagnosis is the most important prognostic factor for PSIs. Although blood tests (i.e. ESR, CRP, and white blood cell count) and imaging studies (most commonly MRI) can be useful, it must be clear to the clinician that diagnostic modalities, either tissue biopsy or blood cultures, are of the utmost importance for diagnosing PSIs and devising a correct antibiotic therapy. Antibiotic therapy with early bracing (or bed rest) is the most commonly used treatment method for PSIs. Nevertheless, a more aggressive surgical treatment may be required in some patients. The goals of surgical treatment are to help the eradication of the infection, provide an adequate wound closure, and maintain spine column mechanical stability.

Surgical treatment of tuberculous spondylodiscitis.

BACKGROUND: Most patients affected by spinal tuberculosis can be successfully treated conservatively with chemotherapy, external bracing and prolonged rest. Nevertheless, kyphotic deformity, spinal instability and neurological deficit remain a common complication associated with conservative approach. AIM: To illustrate different indications and treatment modalities for tuberculous spondylodiscitis, focusing on the role of surgery as an adjuvant of effective chemotherapy in the management of selected patients. MATERIALS AND METHODS: Various early and late surgical procedures are recommended to treat spinal tuberculosis. The Authors analyzed surgical indications, approaches, complications and outcomes comparing their experience with available Literature. RESULTS: Conservative management is preferable in patients without vertebral instability and deformity; in presence of abscesses, invasive radiological techniques in combination with abscess drainage and chemotherapy are recommended. In patients with vertebral collapse, kyphotic deformity or abscess formation, vertebral instability or neurological deficits, anterior radical debridement, anterior strut grafting and anterior instrumentation is an optimal standardized procedure. In patients with involvement of more than two vertebral levels or lumbosacral junction and in those whose sagittal alignment is markedly deformed with segmental kyphosis, and in patients who have difficulty in undergoing anterior instrumentation, posterior instrumentation is recommended in combination with anterior radical debridement and anterior strut grafting in one or two staged procedures. CONCLUSIONS: Since surgery for spinal tuberculosis is demanding, it should be performed only after taking into account the risks and benefits in operable patients. Various surgical procedures are recommended to treat spinal tuberculosis but the common goals are to eradicate the infection and to prevent or to treat neurologic deficits or spinal deformity.

Spine degeneration in a murine model of chronic human tobacco smokers.

OBJECTIVE: To investigate the mechanisms by which chronic tobacco smoking promotes intervertebral disc degeneration (IDD) and vertebral degeneration in mice. METHODS: Three month old C57BL/6 mice were exposed to tobacco smoke by direct inhalation (4 cigarettes/day, 5 days/week for 6 months) to model long-term smoking in humans. Total disc proteoglycan (PG) content [1,9-dimethylmethylene blue (DMMB) assay], aggrecan proteolysis (immunobloting analysis), and cellular senescence (p16INK4a immunohistochemistry) were analyzed. PG and collagen syntheses ((35)S-sulfate and (3)H-proline incorporation, respectively) were measured using disc organotypic culture. Vertebral osteoporosity was measured by micro-computed tomography. RESULTS: Disc PG content of smoke-exposed mice was 63% of unexposed control, while new PG and collagen syntheses were 59% and 41% of those of untreated mice, respectively. Exposure to tobacco smoke dramatically increased metalloproteinase-mediated proteolysis of disc aggrecan within its interglobular domain (IGD). Cellular senescence was elevated two-fold in discs of smoke-exposed mice. Smoke exposure increased vertebral endplate porosity, which closely correlates with IDD in humans. CONCLUSIONS: These findings further support tobacco smoke as a contributor to spinal degeneration. Furthermore, the data provide a novel mechanistic insight, indicating that smoking-induced IDD is a result of both reduced PG synthesis and increased degradation of a key disc extracellular matrix protein, aggrecan. Cleavage of aggrecan IGD is extremely detrimental as this results in the loss of the entire glycosaminoglycan-attachment region of aggrecan, which is vital for attracting water necessary to counteract compressive forces. Our results suggest identification and inhibition of specific metalloproteinases responsible for smoke-induced aggrecanolysis as a potential therapeutic strategy to treat IDD.

Bioplasty for vertebral fractures: preliminary results of a pre-clinical study on goats using autologous modified skin fibroblasts.

The debate is still ongoing about the long term effects of the mininvasive vertebral augmentation techniques and their usefulness in treating more complex cases where a bone inducing effect more than a merely bone substitution would be suitable, such as the vertebral fractures in young patients. We previously developed a clinically relevant gene therapy approach using modified dermal fibroblasts for inducing bone healing and bone formation in different animal models. The aim of this study is to show the feasibility of a minimally invasive percutaneous intrasomatic ex vivo gene therapy approach to treat thoracolumbar vertebral fractures and anterior column bone defects in a goat model.