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Journal of Pediatric Orthopedics. Part B Jul 2024Cerebral palsy (CP) is a heterogeneous group of disorders with different clinical types and underlying genetic variants. Children with CP are at risk for fragility...
Cerebral palsy (CP) is a heterogeneous group of disorders with different clinical types and underlying genetic variants. Children with CP are at risk for fragility fractures secondary to low bone mineral density, and although bisphosphonates are prescribed for the treatment of children with bone fragility, there is limited information on long-term bone impact and safety. Children with CP usually present overtubulated bones, and the thickening of cortical bone by pamidronate treatment can potentially further narrow the medullary canal. Our purpose was to report bone alterations attributable to pamidronate therapy that impact orthopedic care in children with CP. The study consisted of 41 children with CP treated with pamidronate for low bone mineral density from 2006 to 2020. Six children presented unique bone deformities and unusual radiologic features attributed to pamidronate treatment, which affected their orthopedic care. The cases included narrowing of the medullary canal and sclerotic bone, atypical femoral fracture, and heterotopic ossification. Treatment with bisphosphonate reduced the number of fractures from 101 in the pretreatment period to seven in the post-treatment period ( P < 0.001). In conclusion, children with CP treated with bisphosphonate have a reduction in low-energy fractures; however, some fractures still happen, and pamidronate treatment can lead to bone alterations including medullary canal narrowing with sclerotic bone and atypical femoral fractures. In very young children, failure to remodel may lead to thin, large femoral shafts with cystic medullary canals. More widespread use of bisphosphonates in children with CP may make these bone alterations more frequent. Level of evidence: Level IV: Case series with post-test outcomes.
Topics: Humans; Pamidronate; Cerebral Palsy; Child; Female; Male; Bone Density Conservation Agents; Child, Preschool; Bone Density; Retrospective Studies; Adolescent
PubMed: 37811568
DOI: 10.1097/BPB.0000000000001136 -
Cureus Aug 2023Hypercalcemia of malignancy (HCM) is an important cancer-related medical emergency. It is a sign of advanced disease with a poor prognosis. We report a case of a...
Hypercalcemia of malignancy (HCM) is an important cancer-related medical emergency. It is a sign of advanced disease with a poor prognosis. We report a case of a 55-year-old man who presented with decreased sensorium, constipation for 4 days, dysphonia, and weight loss for the past three months. The physical examination showed a petrous nodular lesion of the neck in relation to the right sternocleidomastoid muscle. The digital rectal examination showed an enlarged prostate with a nodule of hard consistency. The blood revealed a hypercalcemia of 18.9 mg/dl and a prostate-specific antigen of 319.18 ng/ml. After further investigation, we discovered a squamous cell carcinoma of the larynx with multiple osteolytic bone lesions and a prostate adenocarcinoma. The hypercalcemia was treated with sodium pamidronate with good results. Such severe hypercalcemia demanded further research which revealed that not only the osteolytic lesions contributed to the elevation of calcium serum levels but also the tumor secretion of parathyroid hormone-related protein. This case highlights the importance of not only having a high suspicion for malignancy in patients presenting with hypercalcemia but also being aware of possible additional diagnoses in a patient with an already identified primary pathology.
PubMed: 37772252
DOI: 10.7759/cureus.44272 -
Frontiers in Immunology 2023Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure...
Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.
Topics: Humans; HIV Infections; HIV-1; Virus Activation; Virus Latency; Alendronate; HIV Seropositivity
PubMed: 37744358
DOI: 10.3389/fimmu.2023.1219250 -
Bone Dec 2023Fluoroquinolone antibiotics are known to induce serious tendinopathies and ligament disorders (TPLDs) on rare occasion, but it is less well-appreciated whether such...
Fluoroquinolone antibiotics are known to induce serious tendinopathies and ligament disorders (TPLDs) on rare occasion, but it is less well-appreciated whether such adverse reactions result from the use of bisphosphonates (BPs). In this study, we assessed the correlation between TPLDs and the use of BPs via U.S. FDA Adverse Event Reporting System (FAERS) database. Bayesian and nonproportional analyses were applied to data retrieved from the FAERS database from the first quarter of 2004 to the third quarter of 2022. A total of 3202 reported cases of TPLDs were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, zoledronate), with statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC). Alendronate showed the highest association with tendinopathies and ligament disorders (ROR = 16.30, PRR = 15.47, IC = 3.88), while zoledronate had the lowest association (ROR = 2.13, PRR = 2.12, IC = 1.08), which was consistent with the results of top 10 preferred terms (PTs) under the narrow standardized MedDRA queries (SMQs) sorted by frequency of reports. Excluding zoledronate, over half of patients who reported BP-related TPLDs were hospitalized, either briefly or extendedly. This was especially true for alendronate, which showed the highest rate of hospitalization (83.25 %), however, the mortality rate reported by those taking alendronate were significantly lower than those of zoledronate and pamidronate. In addition, the clinical characteristics of BP-related TPLDs was analyzed. It is more common to reported in middle-aged and elderly females, the highest proportion was in 50-69 years old. Except for osteoporosis, osteopenia, and osteoporosis prophylaxis, cancer bone metastasis was also the indication of some BPs. The most often reported concomitant/prior medicines were calcium supplements, another BPs, antitumor agents, and nonsteroidal anti-inflammatory drugs. In conclusion, we provide a comprehensive overview of the correlation and clinical characteristics, and prognosis of BP-related TPLDs deserving continued surveillance and appropriate management.
PubMed: 37739298
DOI: 10.1016/j.bone.2023.116919 -
Calcified Tissue International Nov 2023Hepatitis C-associated osteosclerosis (HCAO) is a very rare condition that can be observed in a small number of patients with Hepatitis C Virus (HCV) infection. HCAO is...
Hepatitis C-associated osteosclerosis (HCAO) is a very rare condition that can be observed in a small number of patients with Hepatitis C Virus (HCV) infection. HCAO is usually characterized by widespread bone sclerosis, associated with severe bone pain, and increased levels of bone turnover markers, especially alkaline phosphatase (ALP). In this report, we present the case of a 55-year-old woman who was affected by HCV and came to our attention for severe and diffuse bone pain. Radiological studies showed bone sclerosis, and bone mineral density (BMD) was markedly increased, as well as serum ALP levels. The patient was initially treated with intravenous pamidronate, which provided only a transient benefit on clinical symptoms. Then antiviral therapy for HCV (interferon-alfa and ribavirin) was started and it was effective in making the viral load undetectable. After a long follow-up period, we observed a persistent remission of bone pain, a reduction in BMD together with a progressive trend toward the normalization of bone turnover markers. In conclusion, HCAO, although rare, should be considered among the potential causes of increased bone mass in patients with HCV infection, and treatment for the underlying infection may be effective in controlling the manifestations of this disease.
Topics: Female; Humans; Middle Aged; Antiviral Agents; Follow-Up Studies; Hepacivirus; Hepatitis C; Osteosclerosis; Pain; Sclerosis
PubMed: 37718324
DOI: 10.1007/s00223-023-01135-7 -
Dental Clinics of North America Oct 2023Multiple myeloma (MM) is a hematologic malignancy belonging to a class of disorders known as plasma cell dyscrasias. Common oral manifestations of MM include osteolytic... (Review)
Review
Multiple myeloma (MM) is a hematologic malignancy belonging to a class of disorders known as plasma cell dyscrasias. Common oral manifestations of MM include osteolytic lesions in the mandible and maxilla that can present as painful bony swellings, epulis formation, or sudden teeth movement. MM treatment is coordinated by a multidisciplinary team and is dependent upon the age and physical fitness of the patient, as well as the staging of the disease. A large proportion will be treated with intravenous bisphosphonates, such as pamidronate and zoledronic acid, which places the patients at high risk for developing medication-related osteonecrosis of the jaw (MRONJ).
Topics: Humans; Multiple Myeloma; Mouth; Face; Zoledronic Acid; Pain
PubMed: 37714618
DOI: 10.1016/j.cden.2023.05.014 -
Journal of Bone and Mineral Research :... Nov 2023Bisphosphonates are first-line treatments for several bone and mineral disorders. Studies have reported an increased incidence of serious atrial fibrillation in patients... (Meta-Analysis)
Meta-Analysis
Bisphosphonates are first-line treatments for several bone and mineral disorders. Studies have reported an increased incidence of serious atrial fibrillation in patients receiving bisphosphonates; however, uncertainty remains as to whether electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting electrocardiogram (ECG) findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE from inception until January 14, 2023, for studies reporting ECG parameters after intravenous bisphosphonate infusion. We excluded studies that only reported atrial fibrillation. Study quality was assessed using the Newcastle-Ottawa scale. Continuous data were meta-analyzed if reported in at least two studies. Random-effects models were fitted and reported as standardized mean difference (SMD) with 95% confidence intervals (95% CIs). We found 1083 unique records, of which 11 met our inclusion and exclusion criteria. Studies had a low to low/moderate risk of bias. Six prospective cohort studies were included in the meta-analysis. Five studies used zoledronic acid, whereas one study used pamidronate. Most studies (n = 4) were conducted in postmenopausal women with osteoporosis, one study was conducted in patients with bone metastases, and one study in children with osteoporosis secondary to cerebral palsy. Study populations ranged from n = 15 to n = 116. Heart rate-corrected QT (QTc) was significantly longer post-infusion (SMD = 0.46 ms [95% CI 0.80 to 0.11]; n = 67 patients, k = 2 studies, τ = 0). There were no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc, QTc (maximum), QTc (minimum), and QTc dispersion. The correlation between pre- and post-infusion QTc was not significant (p = 0.93). Overall, there is a weak association between intravenous bisphosphonate infusion and a QTc interval prolongation. However, there is insufficient evidence to support an association between intravenous bisphosphonate and any ECG variable changes, which may precipitate atrial fibrillation. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Child; Humans; Female; Diphosphonates; Bone Density Conservation Agents; Atrial Fibrillation; Prospective Studies; Osteoporosis; Electrocardiography; Minerals
PubMed: 37681243
DOI: 10.1002/jbmr.4911 -
Cureus Aug 2023Significant hypercalcaemia can occur in intensive care unit (ICU) patients. Immobilisation hypercalcaemia has been infrequently reported after ICU admission. Patients,...
Significant hypercalcaemia can occur in intensive care unit (ICU) patients. Immobilisation hypercalcaemia has been infrequently reported after ICU admission. Patients, therefore, usually require extensive workup to rule out other common causes of hypercalcaemia, such as hyperparathyroidism. A case series of five patients who were diagnosed with hypercalcaemia due to immobilisation and received treatment with pamidronate between 2019 and 2023 were reported. The majority of cases were assessed as having hypercalcaemia due to immobilisation in the setting of low to normal parathyroid hormone levels, no suspicion of malignancy, and absence of other possible causative factors. Treatment with pamidronate started 10 to 60 days after hypercalcaemia was identified, and one or two doses of 30 mg of pamidronate were successful in resolving it. Immobilisation hypercalcaemia following ICU admission was uncommon but treatable with pamidronate.
PubMed: 37680410
DOI: 10.7759/cureus.43070 -
Cureus Aug 2023The parathyroid gland is responsible for the synthesis and secretion of parathyroid hormone, which is synthesized and released at an inverse relationship to the level of...
The parathyroid gland is responsible for the synthesis and secretion of parathyroid hormone, which is synthesized and released at an inverse relationship to the level of ionized calcium in the blood. Primary hyperparathyroidism affects women more than men. There are various causes for hyperparathyroidism-induced hypercalcemia and the most common cause is parathyroid adenoma. A less common cause of vitamin D-mediated parathyroid hormone-independent hypercalcemia is the loss of function mutation of the gene. The gene encodes the vitamin D 24-hydroxylase enzyme, responsible for hydroxylating the active form of vitamin D into an inactive form, and mutations in the gene can lead to elevated active vitamin D metabolite levels. It can result in hypercalcemia and hypercalciuria-related complications. We present a case of a 72-year-old male patient referred to the endocrine clinic, who had repeated treatments for hypercalcemia and recurrent renal calculi. He underwent ultrasound, computerized tomography, and sestamibi scans, all reported as normal. Following this, the patient underwent a positron emission tomography (PET) scan, which was also normal. He then finally underwent genetic testing and tested positive for the gene. He was started on fluconazole 50mg once a day and cinacalcet 30mg twice with normalization of calcium level. Three of his family members also tested positive for the condition.
PubMed: 37664318
DOI: 10.7759/cureus.42811 -
Reviews in Endocrine & Metabolic... Dec 2023Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim... (Meta-Analysis)
Meta-Analysis Review
Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI -31.9, -12.1] in the parameters of bone formation after 6-12 months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R = 0.08, p < 0.0001) and formation parameters (R = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.
Topics: Humans; Bone Density Conservation Agents; Fibrous Dysplasia, Polyostotic; Diphosphonates; Fibrous Dysplasia of Bone; Bone Resorption; Pain
PubMed: 37632645
DOI: 10.1007/s11154-023-09832-2