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Rheumatologic diseases and antiphospholipid syndrome
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Thomas J. Santoro, Michiyo Tomita, Alfonse T. Masi
Bisphosphonates are frequently used to prevent glucocorticoid-induced osteoporosis in a number of autoimmune diseases. In a small study (n=21), exposure to these drugs during the first trimester did not increase the risk of abortion, birth defects, or growth retardation relative to controls (45). This notwithstanding, bisphosphonates have a half-life of approximately 10 years (in bone), may be mobilized during pregnancy, and have been shown in experimental studies to cross the placenta and accumulate in the fetus. Given the limited amount of data available on this class of drugs, use of bisphosphonates in pregnancy is not advised.
Multiple myeloma
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Central venous catheters represent a potential source of bacteraemia (182). Melphalan is associated with increased risk of pancytopaenia, mucositis, and pulmonary complications (183–186). Conventional radiography and CT scanning are appropriate imaging investigations. High doses of corticosteroids may cause spinal fractures and avascular necrosis of the femoral heads (amongst other bones). MRI is useful for assessing both of these conditions. Abdominal discomfort resulting from constipation is a well-recognized side effect of thalidomide and can be readily assessed radiologically using a supine plain radiograph of the abdomen. A further reported side effect is interstitial pneumonitis, which can be identified on high-resolution CT (187). The drug bortezomib is associated with cytopaenia, and a decrease in platelet count to <50 000 mm3 occurs in almost 30% of patients, increasing the risk of haemorrhage (188). Other reported adverse effects are sensory neuropathy and pseudomembranous colitis (189). Side effects of intravenous bisphosphonates and newer bone modifying agents include acute-phase reactions, inflammatory reactions at the injection site, hypocalcaemia, hypophosphataemia, renal impairment, osteonecrosis of the jaw, and atypical fractures of the femur (190–194). Regular dental checkups in association with an orthopantomogram and a CT scan enable early diagnosis of osteonecrosis of the jaw (195). Peripheral neuropathy is a significant complication of multiple myeloma that can be caused by the disease itself or by certain therapies including thalidomide and bortezomib (54).
Role of bisphosphonates and denosumab
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Blossom Samuels, Yi Liu, Joseph Lane
Bisphosphonates are a class of agents that have been widely used as the first-line treatment of osteoporosis and a number of other conditions involving excessive bone resorption, including skeletal complications of malignancy, osteogenesis imperfecta, and Paget disease. Etidronate, the first bisphosphonate approved in the United States, was used in 1968 to treat a young patient with myositis ossificans progressive. Etidronate was considered to also have several other potential benefits, including the capacity to prevent heterotopic ossification after total hip replacement and spinal cord injury. Then, in the 1970s, with more bisphosphonates available, these medications were employed to treat a number of conditions such as Paget disease and hypercalcemia of malignancy. In the 1990s, after bone densitometry use widened, bisphosphonates became standard treatment for patients diagnosed with osteoporosis. For more than 40 years, bisphosphonates have been used worldwide for the treatment of osteoporosis (6).
Risedronate-loaded aerogel scaffolds for bone regeneration
Published in Drug Delivery, 2023
Nahla El-Wakil, Rabab Kamel, Azza A. Mahmoud, Alain Dufresne, Ragab E. Abouzeid, Mahmoud T. Abo El-Fadl, Amr Maged
In this study, the fabricated 3D aerogel scaffolds were used as a carrier for risedronate. Bisphosphonates are therapeutic agents used for the treatment of bone disorders. The regular turnover of bone is maintained by a balance between the actions of osteoblasts (cells that build bone) and osteoclasts (bone destroying cells). Bisphosphonates decrease bone loss by inhibiting the action of osteoclasts (Weinstein et al., 2009). Loading the scaffolds with a drug inhibiting bone resorption like bisphosphonates can optimize the treatment of bone defects. Therefore, cellulose-based 3D aerogel scaffolds, loaded with risedronate, were prepared by chemical cross-linking (with amorphous cellulose) or physical cross-linking (with chitosan), and they were evaluated for their physicochemical and cell regenerative properties.
Treatment of fibrous dysplasia: focus on denosumab
Published in Expert Opinion on Biological Therapy, 2022
Bogdan Huzum, Sabina Antoniu, Raluca Dragomir
Diagnosis is more straightforward in MAS than in monostotic FD and is made based on bone, cutaneous, and endocrinologic manifestations. In isolated FD, molecular diagnostics and a thorough differential are needed to confirm the diagnosis [6]. Molecular diagnosis is generally made in bone biopsy by identifying the mutated Gs protein. The management of FD/MAS involves non-pharmacological and pharmacological interventions. Non-pharmacological interventions should focus on patient education and information on the nature of the disease, lifestyle changes in the context of exercise and rehabilitation, and orthopedic interventions. Pharmacological interventions can include treatment of symptoms, antiresorptive interventions, supplemental administration of phosphorus and vitamin D, and treatment of endocrinological conditions. Symptom treatment is focused on pain, which is the main symptom of the disease and a significant reason for impaired quality of life [6]. Antiresorptive interventions are mostly used in the treatment of postmenopausal osteoporosis and include bisphosphonates or denosumab. Bisphosphonates are commonly used based on a larger body of evidence for clinical efficacy. Denosumab use in FD/MAS is only reported in isolated cases or in small series. This review discusses the scientific rationale for using denosumab in FD/MAS and existing clinical evidence.
Premenopausal osteoporosis
Published in Climacteric, 2022
Clinical trials, some specifically studying premenopausal women, provide evidence for efficacy of bisphosphonates based on short-term improvement in BMD in several forms of secondary osteoporosis as well as in idiopathic osteoporosis (see Table 5) [37–50]. Data on fracture risk reduction remain lacking. The long half-life and skeletal accumulation of bisphosphonates remain a concern in young, reproductive-aged women where the safety of these drugs in pregnancy has not been adequately studied and transplacental passage has been observed in animal studies (FDA Category C rating for oral forms, Category D for zoledronic acid) [48–50]. The majority of the literature regarding bisphosphonate use in humans, however, does not report severe adverse fetal and maternal events [51,52] and no increased rate of congenital malformations has been noted [53]. Bisphosphonates are recommended only in the high-risk patient, are best avoided in the setting of a planned pregnancy within the next 12 months [54] and are best used for the shortest possible duration. FDA approval of bisphosphonate use in premenopausal women is confined to those on sustained glucocorticoid therapy at high risk of fracture.