The Rationale for Using Neridronate in Musculoskeletal Disorders: From Metabolic Bone Diseases to Musculoskeletal Pain

Neridronate or ((6-amino-1-hydroxy-1-phosphonohexyl) phosphonic acid) is an amino-bisphosphonate (BP) synthetized in Italy in 1986. Bisphosphonates are molecules with a P-C-P bond in their structure that allows strong and selectively binding to hydroxyapatite (HAP) as well as osteoclasts inhibition through different mechanisms of action. Neridronate was initially used to treat Paget disease of the bone, demonstrating effectiveness in reducing bone turnover markers as well as pain. The interesting molecular properties of neridronate foster its wide use in several other conditions, such as osteogenesis imperfecta, and osteoporosis. Thanks to the unique safety and efficacy profile, neridronate has been used in secondary osteoporosis due to genetic, rheumatic, and oncological diseases, including in pediatric patients. In the last decade, this drug has also been studied in chronic musculoskeletal pain conditions, such as algodystrophy, demonstrating effectiveness in improving extraskeletal outcomes. This review highlights historical and clinical insights about the use of neridronate for metabolic bone disorders and musculoskeletal pain conditions

Transient osteoporosis of the hip and subclinical hypothyroidism: an unusual dangerous duet? Case report and pathogenetic hypothesis

Background: Transient osteoporosis of the hip (TOH) is a rare and temporary clinical condition characterised by bone marrow edema (BME), severe pain, and functional limitation. It commonly occurs in middle-aged men or in women in the last trimester of pregnancy. TOH usually resolves with conservative therapy but may predispose to hip fracture or progression to avascular necrosis (AVN). Etiology is still unclear, although several pathophysiological mechanisms underpinning this condition has been proposed. We describe the management of an unusual case of TOH occurred in a patient with subclinical hypothyroidism. Case presentation: A clinical case of a 46-year-old man with severe pain in the left anterior thigh is presented. After a comprehensive clinical and radiological approach, a TOH was diagnosed. Moreover, biochemical assessment suggested the presence of subclinical hypothyroidism. After 3 months of treatment with clodronate, physical therapy and hormone replacement therapy (HRT) a significant improvement of clinical and radiological outcomes was observed. Conclusion: Several pathological conditions have been related to development of TOH. In our case, we suggested for the first time a role of subclinical hypothyroidism as novel contributory factor for the onset of this condition, providing pathophysiological mechanisms and a scientific rationale for pharmacological treatment

Complex Regional Pain Syndrome Type I Following Non-Orthopedic Surgery: Case Report and Narrative Review

Complex regional pain syndrome type I (CRPS I)—or algodystrophy—is a rare disease that usually occurs after a traumatic event. It is characterized by typical clinical findings such as severe and disabling pain disproportionate to the injury, functional limitations, as well as sensory and vasomotor alterations. However, some people do not report any injury associated with algodystrophy onset in personal history. We describe the management of an unusual case of CRPS I which occurred during the long-term follow-up of percutaneous transluminal coronary angioplasty (PTCA) and performed a narrative review of algodystrophy in non-orthopedic surgery. A clinical case of a 44-year-old man with a spontaneous onset of CRPS I of the right ankle is presented. He did not refer to history of any memorable significant trigger event. Approximately 5 months before the onset of clinical manifestations, he received a PTCA via the right femoral approach. We suppose an association between CRPS and this procedure and propose a possible pathophysiologic mechanism. The patient was treated with intramuscular neridronate, which resulted in significant pain relief and improved his quality of life. A comprehensive clinical and instrumental evaluation in patients with CRPS is challenging but mandatory for a correct diagnosis. An extensive analysis of patient history is important for identifying any potential trigger event, including non-orthopedic procedures. Bone scan could have a pivotal role for improving diagnostic sensitivity and specificity in CRPS I. Neridronate was a safe and effective therapeutic approach for this patient, confirming the results of the high-quality evidence availabl

Characterization of neuropathic component of back pain in patients with osteoporotic vertebral fractures

BACKGROUND: Osteoporotic vertebral fractures (OVFs) are often followed by chronic back pain which may have a nociceptive, neuropathic, or mixed component. However, literature on this topic is lacking. OBJECTIVE: The objective of this cross-sectional study is to characterize the neuropathic component of chronic back pain in patients with OVFs. METHODS: Spine fractures were detected by morphometric examination. Pain severity and its impact on daily living activities (ADL) were evaluated through the Brief Pain Inventory (BPI). Neuropathic pain was investigated through the Italian Versions of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS) and the painDETECT questionnaire (PD-Q). RESULTS: We included 72 patients, mainly women (88.8%), with mean age of 69.2 years. The 70.8% of patients had multiple OVFs, of which 47% located at the thoracic spine, 43.1% at the thoracic and at lumbar spine, and 9.8% at the lumbar spine. The BPI showed moderate back pain in 23.6% of cases and severe in 8.3% of cases, with high interference with ADL in 38.9% of patients. The PD-Q revealed the presence of neuropathic pain in 5.5% of cases, while the S-LANSS in 23.6% of cases. CONCLUSIONS: In our study, the prevalence of neuropathic component of chronic back pain ranged from 5.5% to 23.6%, according to PD-Q and LANSS respectively, in patients with OVFs. Further studies should investigate if the characterization of chronic back pain might contribute to appropriateness of interventions for this population

Effectiveness of High-Intensity Laser Therapy Plus Ultrasound-Guided Peritendinous Hyaluronic Acid Compared to Therapeutic Exercise for Patients with Lateral Elbow Tendinopathy

Lateral elbow tendinopathy (LET) is a common painful musculoskeletal disorder. Several treatments have been proposed to provide pain reduction and functional recovery, including laser therapy, hyaluronic acid peritendinous injection (Hy-A), and therapeutic exercise (TE). Our study aims to assess the effectiveness of a combined approach with high-intensity laser therapy (HILT) and Hy-A injections compared to TE on pain, muscle strength, and disability in patients with painful LET. A retrospective longitudinal study was carried out by consulting the medical records of patients with a diagnosis of painful LET formulated by clinical and instrumental findings that received functional evaluations, including the Patient-Rated Tennis Elbow Evaluation (PRTEE) and muscle strength measurement at least four times: T0 (“baseline”), 1-month (T1), 3-month (T2), and 6-month follow-ups (T3). Medical records of 80 patients were analyzed. In the HILT + HyA group, the Peak-strength (p < 0.001) and mean strength (p < 0.001) significantly increased compared to the TE group between study times. For the PRTEE-total-score as for the subscales, the HILT + HyA group reported statistically significant reductions only for the comparisons of baseline versus T1 and baseline versus T2. No serious adverse events occurred. Our findings suggest that Hy-A associated with HILT might be more effective than TE for people with LET in the short–medium term