Nanocarrier armor for siRNA delivery to address fracture risk in osteoporosis

Secondary Causes of Osteoporosis

Gene Silencing via RNAi and siRNA Quantification in Tumor Tissue Using MEND, a Liposomal siRNA Delivery System

Synergistic Silencing: Combinations of Lipid-like Materials for Efficacious siRNA Delivery

Report of a Muscular Dystrophy Campaign funded workshop Birmingham, UK, January 16th 2004. Osteoporosis in Duchenne muscular dystrophy; its prevalence, treatment and prevention

Strategies for the prevention and treatment of osteoporosis during early postmenopause

Strontium ranelate and fluoride salts are therapeutic options to reduce fracture risk in osteoporosis. Incorporation of these elements in the physiological hydroxyapatite matrix of bone is accompanied by changes in bone remodeling, composition, and structure. However, a direct comparison of the effectiveness of strontium and fluoride treatment in human cortical bone with a focus on the resulting mechanical properties remains to be established. Study groups are composed of undecalcified specimens from healthy controls, treatment-naïve osteoporosis cases, and strontium ranelate or fluoride-treated osteoporosis cases. Concentrations of both elements were determined using instrumental neutron activation analysis (INAA). Backscattered electron imaging was carried out to investigate the calcium content and the cortical microstructure. In comparison to osteoporotic patients, fluoride and strontium-treated patients have a lower cortical porosity indicating an improvement in bone microstructure. Mechanical properties were assessed via reference point indentation as a measure of bone's resistance to deformation. The strontium-incorporation led to significantly lower total indentation distance values compared to osteoporotic cases; controls have the highest resistance to indentation. In conclusion, osteoporosis treatment with strontium and fluoride showed positive effects on the microstructure and the mechanical characteristics of bone in comparison to treatment-naïve osteoporotic bone. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 433-442, 2017.

Elderly and senile people are characterized by a high prevalence of osteoporosis, which, in turn, increases the risk of fractures, including the repeated ones. Fractures in osteoporosis are an extremely unfavorable complication of the disease, leading to catastrophic consequences in old age. The prevalence of osteoporotic fractures progressively increases with age. At present, the cumulative frequency of hip fractures in women over 80 is about 30%. The proportion of vertebral fractures in women older than 80 years is up to 40% of all vertebral osteoporotic fractures. Despite the tremendous successes achieved in the diagnosis and treatment of osteoporosis, the disease itself and related fractures remain a serious medical, economic and social problem. Prevention of recurrent fractures in geriatric patients is a system of preventive, rehabilitative and therapeutic measures aimed at reducing the risk of falls, choosing an effective therapy, and reducing the risk of recurring fractures. A serious problem in the treatment of osteoporosis in older people is the inefficiency of the antiresorptive therapy due to an age-related decrease in bone formation. There are frequent cases of a continuing decrease in bone density, the occurrence of repeated fractures during ongoing therapy of osteoporosis. Often the therapy of choice in this case is bone-anabolic therapy with teriparatide, which allows one to achieve good results in the accumulation of bone mineral density. In this article, we will present the clinical case of an elderly patient with severe osteoporosis, in which teriparatide became the drug of choice.

Hormone replacement therapy in perimenopausal women with a low dose oral contraceptive preparation: Effects on bone mineral density and metabolism

The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that rediscovering a phenomenon that was first observed more half a century ago will have an important impact on our understanding of how new antifracture treatments work.

Osteoporosis is the chronic condition of bone associated with decreased bone density, quality of bones and increased risks of fractures. Postmenopausal osteoporosis deals with increased bone resorption that results in loss of bone and fragility over 45 years of women. One of the leading causes of postmenopausal osteoporosis is the reduction of estrogen production in the ovaries of females. Lack of estrogen triggers several bone turnover pathways that result in osteoporosis. The drop of estrogen in the postmenopausal transition period, causes more bone resorption as compared to bone formation resulting in postmenopausal osteoporosis. Osteoporotic fractures is the major threat to the health of the women due to postmenopausal osteoporosis and hormone therapy is considered the first line therapy against this disease. To date, several pharmacological and non-pharmacological approaches have been designed to treat postmenopausal osteoporosis. Bone turnover markers help in the monitoring of osteoporosis treatment and in the assessment of fracture risk. Besides these conventional therapies, novel and advanced strategies have been constructed for the treatment of osteoporosis. Probiotics Choice and Ovarian Follicular Pool have opened a new avenue to treat osteoporosis. This review shed light on the biochemical perspective of postmenopausal osteoporosis, novel methods for its treatment, and management therapies to treat postmenopausal osteoporosis.

Osteoporosis (OP) is a widespread age-related disorder marked by decreased bone density and increased fracture risk, presenting a significant public health challenge. Central to the development and progression of OP is the dysregulation of the mechanistic target of the rapamycin (mTOR)-signaling pathway, which plays a critical role in cellular processes including autophagy, growth, and proliferation. The mTOR-autophagy axis is emerging as a promising therapeutic target due to its regulatory capacity in bone metabolism and homeostasis. This review aims to (1) elucidate the role of mTOR signaling in bone metabolism and its dysregulation in OP, (2) explore the interplay between mTOR and autophagy in the context of bone cell activity, and (3) assess the therapeutic potential of targeting the mTOR pathway with modulators as innovative strategies for OP treatment. By examining the interactions among autophagy, mTOR, and OP, including insights from various types of OP and the impact on different bone cells, this review underscores the complexity of mTOR's role in bone health. Despite advances, significant gaps remain in understanding the detailed mechanisms of mTOR's effects on autophagy and bone cell function, highlighting the need for comprehensive clinical trials to establish the efficacy and safety of mTOR inhibitors in OP management. Future research directions include clarifying mTOR's molecular interactions with bone metabolism and investigating the combined benefits of mTOR modulation with other therapeutic approaches. Addressing these challenges is crucial for developing more effective treatments and improving outcomes for individuals with OP, thereby unveiling the therapeutic potentials of targeting the mTOR-autophagy axis in this prevalent disease.

20 - Pharmacologic Therapy

Osteoporosis is a common skeletal disease that leads to increased bone fragility, associated with increased risk of fracture and consequent significant morbidity and mortality, and is a global public health problem. It results from a chronic imbalance in bone remodeling, where bone resorption by osteoclasts exceeds bone formation by osteoblasts. Aging, hormonal changes, comorbidities, and drugs influence the process that leads to osteoporosis. In this review, we delve into the pathogenesis of primary and secondary osteoporosis after a summary of the normal physiology of bone homeostasis. Primary osteoporosis includes postmenopausal osteoporosis, driven largely by estrogen deficiency, and age-related (senile) osteoporosis, associated with reduced bone formation. An insight into male osteoporosis and osteoporosis treatment is also provided. Secondary osteoporosis can derive from underlying conditions, such as endocrine disorders, chronic inflammatory and genetic diseases, or prolonged use of glucocorticoids. Clinically, osteoporosis is often unacknowledged, underlining the importance of early risk assessment and diagnosis. A thorough understanding of the disease, its subtypes, and its underlying pathogenetic mechanisms is essential for early diagnosis and individualized treatment, all targeted to effective fracture prevention.

Biased and allosteric modulation of bone cell-expressing G protein-coupled receptors as a novel approach to osteoporosis therapy

Mechanisms of Ferroptosis in bone disease: A new target for osteoporosis treatment.