Luca Pietrogrande

Teriparatide in the treatment of non-unions: Scientific and clinical evidences

INTRODUCTION Each fracture has a failing risk which can lead to a non-union. Among the non-invasive strategies proposed to improve bone healing, also in non-union, the use of teriparatide, a drug for the treatment of the osteoporosis, has increasing supporting data. EXPERIMENTAL DATA Many studies mainly on rats, but also on primates, demonstrate the positive effect on fracture healing of teriparatide, both in physiological and pathological conditions, with a more rapid evolution of the reparative callus. CLINICAL DATA A double blinded randomized controlled study on wrist fractures demonstrated a positive effect, in term of healing speed, of teriparatide at the dose of 20 μg/day, but not at the higher dose of 40 μg/day. A prospectic randomized study on pelvic fractures showed a faster healing in teriparatide treated patients. The use of teriparatide in non-unions is reported as effective in numerous case report. The effect of teriparatide seems very useful in the non-unions consequent to an atypical femoral fracture after long-term administration of bisphosphonates. CONCLUSIONS A conceivable positive effect of teriparatide on fracture healing is well-documented on animals, and very likely on humans, however further studies are needed to confirm these hopeful hypotheses.

Recognition of Morphometric Vertebral Fractures by Artificial Neural Networks: Analysis from GISMO Lombardia Database

Background It is known that bone mineral density (BMD) predicts the fractures risk only partially and the severity and number of vertebral fractures are predictive of subsequent osteoporotic fractures (OF). Spinal deformity index (SDI) integrates the severity and number of morphometric vertebral fractures. Nowadays, there is interest in developing algorithms that use traditional statistics for predicting OF. Some studies suggest their poor sensitivity. Artificial Neural Networks (ANNs) could represent an alternative. So far, no study investigated ANNs ability in predicting OF and SDI. The aim of the present study is to compare ANNs and Logistic Regression (LR) in recognising, on the basis of osteoporotic risk-factors and other clinical information, patients with SDI≥1 and SDI≥5 from those with SDI = 0. Methodology We compared ANNs prognostic performance with that of LR in identifying SDI≥1/SDI≥5 in 372 women with postmenopausal-osteoporosis (SDI≥1, n = 176; SDI = 0, n = 196; SDI≥5, n = 51), using 45 variables (44 clinical parameters plus BMD). ANNs were allowed to choose relevant input data automatically (TWIST-system-Semeion). Among 45 variables, 17 and 25 were selected by TWIST-system-Semeion, in SDI≥1 vs SDI = 0 (first) and SDI≥5 vs SDI = 0 (second) analysis. In the first analysis sensitivity of LR and ANNs was 35.8% and 72.5%, specificity 76.5% and 78.5% and accuracy 56.2% and 75.5%, respectively. In the second analysis, sensitivity of LR and ANNs was 37.3% and 74.8%, specificity 90.3% and 87.8%, and accuracy 63.8% and 81.3%, respectively. Conclusions ANNs showed a better performance in identifying both SDI≥1 and SDI≥5, with a higher sensitivity, suggesting its promising role in the development of algorithm for predicting OF.

Update on the efficacy, safety, and adherence to treatment of full length parathyroid hormone, PTH (1-84), in the treatment of postmenopausal osteoporosis.

Full length (1-84) parathyroid hormone (PTH) was introduced in Europe as a treatment for postmenopausal osteoporosis in 2006. The efficacy of PTH (1-84) in the prevention of vertebral fractures is very high, and is similar to that of teriparatide. Its action in the prevention of femoral fractures has yet to be fully demonstrated, but the incidence of such fractures in trials was very low, and a decrease in nonvertebral fractures was seen in high-risk patients. The effect on bone mineral density (BMD) was clearly demonstrated in the spine and also in the hip. The effects on BMD were evident and increased progressively with treatment until 36 months. After its discontinuation there was a clear decrease in BMD if no antiresorptive treatment was initiated. Increases in bone volumetric density and bone volume in trabecular sites were also reported. Moreover, a bone volume increase was detected in cortical sites. Hypercalcemia and hypercalciuria are frequent consequences of PTH treatment, but rarely have clinical effects and are usually well controlled by reducing calcium and vitamin D supplementation.

Assessment of radiological vertebral fractures in HIV‐infected patients: clinical implications and predictive factors

The aim of this study was to evaluate the clinical impact of including lateral spine X‐ray in the screening of bone diseases in HIV‐positive patients.

Functional characterisation of a novel mutation affecting the catalytic domain of MMP2 in siblings with multicentric osteolysis, nodulosis and arthropathy

Multicentric osteolysis, nodulosis and arthropathy (MONA) is a rare autosomal recessive disorder. To date, 13 mutations of the matrix metalloproteinase 2 (MMP2) gene have been detected in 26 patients with MONA and other osteolytic syndromes. Here, we describe the molecular and functional analysis of a novel MMP2 mutation in two adult Italian siblings with MONA. Both siblings displayed palmar-plantar subcutaneous nodules, tendon retractions, limb arthropathies, osteolysis in the toes and pigmented fibrous skin lesions. Molecular analysis identified a homozygous MMP2 missense mutation in exon 8 c.1228G>C (p.G410R), not detected in 260 controls and predicted by several bioinformatic tools to be pathogenic. By protein modelling, the mutant residue was predicted to affect the main chain conformation of the catalytic domain. Gelatin zymography, the gold standard test for MMP2 function, of serum-free conditioned medium from G410R-MMP2-expressing human embryonic kidney (HEK) cells, showed a complete loss of gelatinolytic activity. The novel mutation is located in the catalytic domain, as are 3 (p.E404K, p.V400del and p.G406D) of the other 13 MMP2 mutations described to date; however, p.G410R underlies a phenotype that is only partially overlapping that of other MMP2 exon 8 mutation carriers. Our results further delineate the complexity of genotype–phenotype correlations in MONA, broaden the repertoire of reported MMP2 mutation and enhance the comprehension of the protein motifs crucial for MMP2 catalytic activity.

Conservative treatment of a femoral neck fracture following nail removal.

With increased longevity, the management of fragility fractures in the elderly is becoming more frequent. In particular, hip fractures have considerable importance due to the significant morbidity and mortality. A 67-year-old woman underwent intramedullary nail (IMN) removal inserted for a pertrochanteric fracture that had occurred 20 months earlier. This was indicated due to continuous discomfort related to the protruding apex of the implant over the great trochanter. Due to pain persistence two days after surgery, a computed tomography (CT) scan was performed, documenting a minimally displaced impacted subcapital femoral neck fracture. Conservative management with close radiographic follow-up was conducted. After six months, the patient had returned to previous daily activities and a satisfactory range of motion was achieved without pain on walking. The purpose of our paper is to discuss the decision of removing hardware in the elderly osteoporotic patient and to analyze the possibility to conservatively treat an impacted minimally displaced subcapital fracture occurring after the removal of an IMN inserted previously for the treatment of a trochanteric fracture. In the elderly population with decreased bone quality, the removal of intramedullary implants of the proximal femur should be carefully evaluated, and osteoporotic patients undergoing reduction and fixation of femoral fractures should be encouraged to start antiosteoporotic therapy (bisphosphonate, teriparatide) to reduce the risk of further bone loss. Conservative treatment should be considered for the management of lesser symptomatic minimally displaced impacted fractures, where the inherent stability of the fracture allows rapid healing without further surgical attempts.

Isolated congenital absence of posterior cruciate ligament? A case report

A rare case of a 28-year-old Asiatic male with the isolated absence of a posterior cruciate ligament is reported. Clinical features, diagnostic steps, therapeutic strategies and follow-up are described. A review of the literature is also presented.

Vertebroplasty and kyphoplasty for the treatment of thoracic fractures in osteoporotic patients: a finite element comparative analysis

Background Vertebral compression fractures occur in the thoracolumbar junction, causing the collapse of the vertebral body. For their treatment, vertebroplasty and kyphoplasty are used, but it is still unknown which technique is to be preferred. Methods Finite element models of the thoracic spine were developed to evaluate the outcomes of vertebroplasty and kyphoplasty. A mild and severe collapse of T10 treated with vertebroplasty or kyphoplasty was studied. Stresses on the endplates and intradiscal pressures were extrapolated to determine the stress distribution in the adjacent structures. Results The validation ensured a correct stiffness and a proper kinematic of each functional spinal unit. The results demonstrated that a consolidation following vertebroplasty caused slight variations of intradiscal pressures and stresses. If a kyphoplasty was performed after a mild collapse of the vertebral body, a 25% stress reduction on endplates was found. In cases of severe collapse, when a partial height restoration was achieved, a 15% stress reduction was obtained, while with a full recovery of the anterior wall of the collapsed vertebra, there was a further reduction of 40%. Conclusions To reduce the stresses on the adjacent endplates and the risk of fracture, the results suggest a kyphoplasty is to be preferred, trying to restore the initial vertebral body height.

Can Clinical and Surgical Parameters Be Combined to Predict How Long It Will Take a Tibia Fracture to Heal? A Prospective Multicentre Observational Study: The FRACTING Study

Background Healing of tibia fractures occurs over a wide time range of months, with a number of risk factors contributing to prolonged healing. In this prospective, multicentre, observational study, we investigated the capability of FRACTING (tibia FRACTure prediction healING days) score, calculated soon after tibia fracture treatment, to predict healing time. Methods The study included 363 patients. Information on patient health, fracture morphology, and surgical treatment adopted were combined to calculate the FRACTING score. Fractures were considered healed when the patient was able to fully weight-bear without pain. Results 319 fractures (88%) healed within 12 months from treatment. Forty-four fractures healed after 12 months or underwent a second surgery. FRACTING score positively correlated with days to healing: r = 0.63 (p < 0.0001). Average score value was 7.3 ± 2.5; ROC analysis showed strong reliability of the score in separating patients healing before versus after 6 months: AUC = 0.823. Conclusions This study shows that the FRACTING score can be employed both to predict months needed for fracture healing and to identify immediately after treatment patients at risk of prolonged healing. In patients with high score values, new pharmacological and nonpharmacological treatments to enhance osteogenesis could be tested selectively, which may finally result in reduced disability time and health cost savings.