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Multiple myeloma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
The Medical Research Council (MRC) Myeloma IX trial showed significant benefits of zoledronic acid over sodium clodronate in reduction of skeletal-related events (27% vs. 35.3%; p = .0004), in overall survival (OS; 50 months vs. 44.5 months; p = .0118) and progression-free survival (PFS; 19.5 months vs. 17.5 months, p = .0179).149 There was, however, a higher incidence of bisphosphonate-associated osteonecrosis of the jaw (BONJ) in the zoledronic acid group (3.5% vs. 0.3%). The benefit in the aforementioned studies was not confined to patients with bone disease at the start of treatment and it is currently recommended that all patients who require treatment for their myeloma should receive a bisphosphonate. Prophylactic bisphosphonates can reduce the extent of skeletal disease in asymptomatic patients but do not delay disease progression and are not currently recommended in current guidelines despite being likely to reduce skeletal-related events. Prolonged administration of zoledronate may be associated with the development of osteonecrosis of the jaw (ONJ) in approximately 4% of the patients. Risk factors included over 36 months of treatment, previous dental surgery and poor dental hygiene. Dental problems should be addressed at an early opportunity before starting zoledronate and patients with ongoing dental problems should probably receive an alternate bisphosphonate. For all bisphosphonates, care should be taken in patients with renal dysfunction and dose modification may be required.
SDH5 down-regulation mitigates the damage of osteoporosis via inhibiting the MyD88/NF-κB signaling pathway
Published in Immunopharmacology and Immunotoxicology, 2023
Hongzi Wu, Dehua Zhang, Haijun Xia, Yongqi Li, Feng Mao, Yi Liao
Osteoporosis is a kind of widespread bone disease in humans. It is a disease with low bone mass and impairment of bone tissue microstructure so as to cause bone fragility, which poses a great threat to the occurrence of fractures [1]. Epidemiological studies suggest that the incidence of osteoporotic fractures may be increasing exponentially in Asia [2]. Osteoporosis is common in women, mainly in postmenopausal women. Postmenopausal osteoporosis is featured by decreased bone mineral density (BMD) and bone microstructure destruction with decreased estrogen levels [3]. The current view is that osteoporosis occurs due to an instable balance between bone formation and bone resorption [4]. The pathogenesis of bone-associated diseases is complex, involving intercellular communication between diverse cells in bone microenvironment, and is regulated by a variety of cytokines [5]. Receptor activator of NF-κB ligand signaling is critical for the proliferation and differentiation of osteoclasts [6,7]. Osteocytes regulate bone mass and homeostasis by noncell autonomous mechanisms affecting bone remodeling, that is, osteoclast-mediated bone resorption followed by osteoblast-mediated bone formation [8]. The bone remodeling without a corresponding increase in bone formation alters the bone trabecular structure and increases fragility of bones [9]. Current drugs used to treat postmenopausal osteoporosis such as bisphosphonates, estrogen, calcitonin, selective estrogen receptor modulators, and recombinant human parathyroid hormone fragments. Adverse effects, such as typical femur fracture, hypercalcemia, thromboembolism, bisphosphonate-associated osteonecrosis of the jaw, vaginal bleeding, and even breast and endometrial cancers, has greatly reduced these drugs’ widespread use [10]. Therefore, safer treatment methods are eagerly needed.