Intravenous Immunoglobulin Shows Beneficial Effects In Post-Menopausal Osteoporosis, Indicating Potential as Treatment

A recent issue of Cirugia y Cirujanos, the official journal of the Mexican Academy of Surgery, published a study that suggests positive benefits of intravenous immunoglobulin (IVIG) on experimentally-induced osteoporosis.¹

The investigators aimed to determine the relationship between post-menopausal osteoporosis (PMO), inflammation, and bone formation and whether any correlation existed between IVIG and bone structure, osteocyte, osteoblast, and osteoclast activity. The study also looked at IVIG’s possible effects on inflammation and the RANKL-beta-catenin pathway.¹

PMO is defined as the association between osteoblastic (bone-building) activity and osteoclastic (bone-resorbing) action. Approximately 50% of women and 30% of men in their 60s and 70s experience osteoporosis, an imbalance of the osteoblastic and osteoclastic activity of cells, which results in the net loss of bone mass.² The hormone estrogen (E2) and the WNT/beta-catenin pathway orchestrate differentiation of monocyte precursor cells into osteoblasts and osteoclasts.¹

The degree of osteocyte differentiation varies depending on the stage of menopause but leads to an overall increase in bone resorption and subsequent bone loss. In addition to an indicator of bone loss and osteoporosis, estrogen is involved in various inflammatory states.¹

Inflammatory disorders of an immune deficiency nature often are accompanied by associated bone loss due to imbalance of osteoblastic and osteoclastic activity. Many patients with autoimmune and chronic inflammatory diseases are treated with IVIG. Although the exact mechanism of action of IVIG is unknown, several pathways diminish autoimmune activity and promote its anti-inflammatory effects.¹

Tumor necrosis factor-alpha (TNF-alpha) has a positive action on osteocytes, leading to bone resorption. RANK (the receptor for RANK-L), TNF factors, and osteoprotegerin (OPG) are all involved in the development of osteocytes. Increases in RANK-L cause decreases in OPG, which is a risk factor for osteoporosis and other bone diseases.¹

The study used 40 female Wistar albino mature rats. All experimentation was performed in accordance with the Animal Ethics Committee, and the subjects were kept under humane conditions with respect to caging, food, temperature, light, dark, and companionship.¹

The researchers performed bilateral oophorectomy on 30 rats, while 10 remained unaltered as a control group. Surgery protocol was followed, including a 3-week healing time, after which those 30 rats were further divided in groups of 10. The control group received no surgery or drug therapy.¹

About the Author

Sandra J. Grillo, MBA, RPh, is a retired independent community pharmacist with more than 40 years of experience. She is currently a student in the University of Connecticut Medical Writing Program.

The 3 surgically-altered groups received different treatments and were further assigned as group 1, 0.9% saline (1mL/kg/day) intraperitoneally; group 2, 17-beta-estradiol (0.5mg/kg), dissolved in sesame oil daily, by gavage (E2); and group 3, IVIG (250mg/kg/day) intraperitoneally. The study continued for 12 weeks.¹

Following the study period, the rats were assessed by DEXA scan for bone mineral density (BMD) using ketamine anesthesia and a “small animal program” method. Areas evaluated were the left proximal femoral shaft and the lumbar vertebrae. Further analysis was performed under animal study protocol to collect blood samples, and subsequent procurement of the left femurs.¹

The femurs were kept in 10% formaldehyde and 10% formic acid. After 28 days, 5 tissue samples per subject were prepared for microscopic morphometric analysis in paraffin blocks, using appropriate dyes, and evaluated for BMD.¹

Measurements in bone integrity of trabecular cell (bone matrix) number, area, thickness, separation and femoral BMD and lumbar vertebral BMD were compared and evaluated with those in the control group. In all categories, measurements for those in the IVIG group were closest to the control, followed by the E2 group and lastly, by the saline group.¹

The measurements of TNF-alpha, IL-6, RANK-L, OPG, and bone marrow beta-catenin were also compared between all 4 groups. The plasma TNF-alpha and IL-6 levels all increased after surgery, but the increase was lowest in the IVIG group. The changes in RANK-L and OPG in the IVIG group also were supportive of less osteoclastic activity.¹

While the study was done on experimentally altered subjects, the results showed positive protective effects of IVIG on osteoporosis. The use of IVIG to treat osteoporosis may have future benefits, with fewer adverse effects than currently available treatment modalities.¹

Intravenous Immunoglobulin Shows Beneficial Effects In Post-Menopausal Osteoporosis, Indicating Potential as Treatment

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REFERENCE

1. Özdemir S, Erbas O. Beneficial effects of IVIG treatment on experimental-induced osteoporosis. Cir Cir. Published online March 19, 2024. doi:10.24875/CIRU.23000219

2. Osteoporosis or Low Bone Mass in Older Adults: United States, 2017-2018. CDC. Updated March 31, 2021. Accessed August 13, 2024. https://www.cdc.gov/nchs/products/databriefs/db405.htm