Osteoporosis
The most prevalent metabolic bone ailment, osteoporosis, which affects 200 million people globally, continues to be a significant issue. Because osteoporosis is a condition that is clinically silent until it manifests as a fracture, it is frequently undertreated and underrecognized.
Osteoporosis, a metabolic bone disease characterized by poor bone density and degeneration of bone architecture that raises the risk of fractures, affects over 10 million men and women in the United States. Osteoporosis-related fractures can raise expenditures for overall health care, cause disability, necessitate nursing home placement, and increase mortality.
Types
1. Primary Osteoporosis
It is frequently linked to ageing and a lack of sex hormones. Age-related osteoporosis is caused by the trabeculae in bone continuously deteriorating. Additionally, postmenopausal women's decreased estrogen production significantly accelerates bone loss. In men, sex-hormone–binding globulin inactivates testosterone and estrogen as ageing signs of progress.
2. Secondary Osteoporosis
Numerous coexisting conditions and drugs can result in secondary osteoporosis. Osteoporosis-related illnesses frequently include physiological processes including calcium, vitamin D, and sex hormones that are out of balance. For instance, it has been discovered that Cushing's syndrome accelerates bone loss by producing too many glucocorticoids. In addition, numerous inflammatory conditions, including rheumatoid arthritis, have been linked to secondary osteoporosis and may call for the patient to receive long-term glucocorticoid therapy. Notably, the most often prescribed drugs thought to cause drug-induced osteoporosis are glucocorticoids.
Screening and Diagnosis
In general, most organizations advise BMD screening for all persons with a history of fractures who are older than 50. The Preventive Services Task Force advises BMD screening for all women 65 years and older, as well as for younger women with fracture risks that are comparable to or higher than those of Caucasian women 65 years and older who are healthy and have no extra risk factors. The Endocrine Society advises screening all males aged 70 years and older as well as men aged 50 to 69 who have significant secondary osteoporosis risk factors.
BMD tests, particularly in the hip and lumbar spine using the dual-energy x-ray absorptiometry (DXA) equipment, or the occurrence of nontraumatic hip or vertebral fractures are used as the gold standard for diagnosing osteoporosis. BMD interpretation and correlation with fracture risk are done using the resulting T-scores. For instance, there is a direct correlation between high fracture risk and low BMD (or a negative T-score).
Another diagnostic tool, named FRAX, was created by the University of Sheffield in Great Britain and is accessible in print or online (Fracture Risk Assessment Tool). The 10-year probability of hip fracture and other major osteoporotic fractures is predicted by considering risk factors like age, race, alcohol use, gender, body mass index, smoking history, prior personal or parental history of fracture, use of glucocorticoids, secondary osteoporosis, rheumatoid arthritis, and femoral neck BMD measurements.
Treatments
1) Antiresorptive agents
Bisphosphonates and denosumab are used as antiresorptive agents to treat osteoporosis. The prevention and/or treatment of osteoporosis in postmenopausal women, males, and/or GIO patients is advised as the first line of treatment with bisphosphonates, except for ibandronate, by AACE/ACE, ACR, NAMS, and the Endocrine Society. By inhibiting osteoclasts from resorbing bone, bisphosphonates bind to the mineral matrix of the bone with a high affinity, reducing bone turnover and increasing bone mass overall. Denosumab is advised by the AACE/ACE as first-line therapy for individuals who are at substantial risk of fracture and who are unable to take oral medication. The first biological drug for the treatment of osteoporosis was denosumab. RANKL is inhibited by this completely human monoclonal antibody, which lowers bone resorption. A transmembrane protein called RANKL is necessary for osteoclast development, survival, and operation.
2) Hormonal Therapies
A) Estrogen Agonists/Antagonists
An EAA known as raloxifene has both agonistic and antagonistic effects on estrogenic pathways.
a) Raloxifene
Raloxifene increases bone mineral density (BMD) by reducing bone resorption and bone turnover in the bone. Additionally, it exerts estrogen-antagonistic effects on uterine and breast tissue.
b) Conjugated Estrogens/Bazodoxifen
In 2013, the FDA approved the use of conjugated estrogen and bazedoxifene combination (Duavee, Pfizer) in postmenopausal women with an intact uterus for the treatment of mild to moderate vasomotor symptoms and the prevention of osteoporosis. As an EAA, bazedoxifene lowers the risk of endometrial hyperplasia brought on by the estrogen component.
c) Estrogen-Progestin Therapy
In terms of managing osteoporosis, estrogen medication is only FDA-approved for preventing osteoporosis in high-risk postmenopausal women and ought to only be used if other non-estrogenic osteoporotic treatments have been deemed ineffective.
B) Testosterone Therapy
The Endocrine Society advises men at substantial risk of fracture to combine anti-fracture therapy with testosterone therapy despite the paucity of evidence on the use of such combinations. When antiosteoporotic therapy is contraindicated and a person's serum testosterone level is less than 200 ng/dL, testosterone monotherapy is advised. It is also advised for people who are at borderline substantial risk for fracture, have serum testosterone levels below 200 ng/dL, and exhibit signs or symptoms of androgen deficiency or hypogonadism.
C) Calcitonin
With characteristics resembling those of the naturally occurring calcitonin found in humans, birds, and fish, calcitonin is a synthetic polypeptide hormone. When other treatments are not practical, the FDA has approved calcitonin for the treatment of osteoporosis in women who have been postmenopausal for more than five years.
Pathophysiology
Bones give the body structure, safeguard the organs, and store minerals like calcium and phosphorus that are crucial for bone growth and stability. At around 30 years of age, people reach their maximal bone mass. Thereafter, individuals gradually start to lose bone mass. Bones undergo constant remodeling throughout life, which involves the resorption of old bone by osteoclasts and its replacement by newly formed bone produced by osteoblasts. This procedure enables mechanical repair and strength maintenance. The pathophysiological alterations seen in osteoporosis may be caused by an imbalance in remodeling activity where resorption is greater than production.
The main way that estrogen and testosterone affect bone remodeling is by preventing bone breakdown. Additionally, cytokines that affect remodeling have been found, such as nuclear factor kappa-B ligand-receptor activator (RANKL). Osteoblasts that attach to the RANK receptors on osteoclasts create RANKL, which causes the osteoclasts to become activated and mature and result in bone resorption. A strong protease known as cathepsin K has been discovered thanks to recent developments in molecular bone biology (CatK). Activated osteoclasts release CatK during the process of bone resorption, which causes the breakdown of the bone matrix and the mineral components of bone tissue. By indirectly promoting osteoblast proliferation by regulating calcium homeostasis, parathyroid hormone (PTH) has a significant impact on bone formation.
Milk Thistle (Silymarin)
With a history spanning more than 2,000 years, milk thistle, technically known as Silybum marianum, is a tribute to the lasting tradition of natural treatments. The active component of the plant, silymarin, which is found in its leaves, seeds, and fruits, is what gives it its therapeutic properties. Milk thistle is mostly known for supporting liver function and has been used to treat liver diseases including cirrhosis and hepatitis C. But when the scientific complexities of this herbal treatment are worked out, we find a range of health advantages that go beyond liver support.
Clinical investigations validate the traditional use of milk thistle as a cytoprotectant for liver illnesses, cancer therapy and prevention, and as a supportive strategy for Amanita phalloides poisoning. Despite the complexity brought about by the varied character of these investigations, milk thistle has an exceptional overall safety profile, with very few reports of major toxicity and adverse effects [1].
Silymarin may be used to prevent or cure infectious infections due to its anti-inflammatory qualities, which also regulate important mediators such as nitrous oxide, interleukins, and tumor necrosis factor (TNF). The preventive effects of cytoprotection are numerous and include growth factor expression enhancement, leukotriene production inhibition, and promotion of neuronal differentiation.
Exploring Health Benefits
· Liver Health: The main benefit of milk thistle is its capacity to assist liver function. Silymarin is thought to protect liver cells from oxidative stress and toxin-induced damage while also promoting liver regeneration.
· Skin Health: Milk thistle contains compounds that may be beneficial to the skin, especially antioxidants. These antioxidants provide a natural method of preserving the vitality of the skin by actively guarding against harm brought on by free radicals.
· Bone Health: New research indicates that milk thistle may be able to improve bone density and stop bone deterioration. The intrinsic anti-inflammatory and antioxidant qualities of silymarin are responsible for this advantage.
· Weight Loss: Milk thistle's capacity to treat variables linked to obesity is the basis for its association with weight loss. Milk thistle may help with weight control by lowering inflammation and insulin resistance.
· Prevention of Cancer: Research indicates that silymarin may have anti-cancer effects, by preventing the proliferation of certain cancer cells. Nevertheless, further investigation is necessary to confirm these first results.
· Support for the immunological System: It has been noted that milk thistle both boosts and calms an overreactive immunological response that is linked to chronic inflammation. Its double function makes it seem like an ally for immune system health in general.
Role of Milk Thistle in Bone Health and Osteoporosis
Because of its many health advantages, silymarin, the active ingredient in milk thistle, has been the focus of scientific research. Beyond its well-known hepatoprotective qualities, silymarin may also be related to bone health, according to current research.
In rats, 2013 research found that milk thistle prevented bone loss brought on by low estrogen, especially in animals whose ovaries had been removed. According to this research, milk thistle may help prevent estrogen-related bone loss, which postmenopausal women often worry about. The findings of the study suggested that milk thistle may have osteoprotective properties.
A progressive skeletal illness, osteoporosis is characterized by a decrease in bone mass, changes in the architecture of the affected bones, and an increased risk of fractures. It mostly affects the trabecular bone and is common in postmenopausal women. The potential of silymarin, a flavonoid-rich substance found in milk thistle with strong antioxidant qualities, for bone health has recently drawn attention. Research, including a mouse model for fracture healing, indicates that supplementing with silymarin improves serum indicators, and bone mineral density, and has estrogenic antiosteoporotic effects. It is a treatment for osteoporosis because of its function in controlling osteogenesis and reducing bone loss, especially in postmenopausal women looking for alternatives to hormone replacement therapy. The creation of a potent estrogen antagonist, such as silymarin, would be very beneficial in halting bone loss without the negative side effects of conventional HRT [3].
Silymarin has a major role in controlling osteogenesis, or the process of making new bones and preventing bone loss. This suggests that milk thistle may have an impact on the processes that lead to bone formation, which makes it a viable option for anti-osteoporotic and fracture-healing treatments. Beyond its hepatoprotective properties, silymarin has several other advantages that are demonstrated by its complex involvement in bone health maintenance.
Additional research on silymarin's impact on bone health has shown that it can stimulate the growth of osteoblasts. Silymarin has been shown to stimulate the activity of osteoblasts, which are important cells involved in bone deposition and may have a beneficial effect on bone development. Silymarin has also been linked to a decrease in bone resorption, the breakdown of bone tissue that results in a rise in bone density. The total preservation and improvement of bone density are facilitated by these two-fold impacts on osteoblasts and bone resorption.
Preclinical and Clinical Trials of Milk Thistle
The potential of milk thistle extract (MTE) and silymarin, a component of MTE, to prevent estrogen deficiency-induced bone loss was examined in preclinical experiments conducted on mice. Ovariectomy-affected mice were used in research as a model for osteopenia following menopause. Oral administration of MTE or silymarin increased the activity of alkaline phosphatase in osteoblasts, decreased tartrate-resistant acid phosphatase (TRAP) in osteoclasts, and increased femoral bone mineral density. The pharmacological synergy between combination treatment with MTE and isoflavone suggested the possibility of osteogenic activity. The findings showed that in preclinical conditions, oral dosages of MTE significantly reversed bone loss caused by estrogen deprivation [4].
Silymarin, a flavonolignan derived from milk thistle, was the subject of clinical research aimed at treating osteoporosis, especially in postmenopausal women. In terms of bone structure, silymarin showed antioxidant qualities as well as estrogenic antiosteoporotic actions. Supplementing with silymarin enhanced tibial healing in a mouse fracture healing model, as evidenced by higher blood levels of osteocalcin and alkaline phosphatase (ALP) and bone mineral density (BMD). According to the investigations, silymarin is essential for controlling osteogenesis, halting bone resorption, and promoting fracture repair. Silymarin may be used as a therapy for osteoporosis in postmenopausal women [5].
Another study looked at how silymarin, celecoxib, and their combination affected rats' osteoarthritis caused by monoiodoacetate (MIA). In synovial tissue, the combination of celecoxib and silymarin showed an additive benefit in lowering oxidative stress and inflammation. When both substances were taken separately, the synovial tissue's levels of nitric oxide and malondialdehyde were reduced, and the cartilage surface was enhanced. According to the study, silymarin's antioxidant-based anti-inflammatory properties may enhance celecoxib's osteoarthritis-relieving benefits [6].
In another study, rats with ovariectomies were used to examine the estrogenic effects and antiosteoporotic activity of silymarin. A potent estrogenic substance called ethinylestradiol (EE) was compared to silymarin in the study. Silymarin stimulated uterine weight without inhibiting body weight increase, exhibiting modest estrogenic actions. It boosted calcium and phosphorus levels, preserved the thickness of the trabecula, and stopped the bone loss brought on by ovariectomy. Its unique feature is highlighted by the fact that silymarin did not lower osteocalcin levels like EE did. According to the study, silymarin may have its protective benefits against bone loss in rats due in part to its estrogenic properties, which may interact with estrogen receptors [7].
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