The role of estrogen in osteoarthritis and lower back pain

Osteoarthritis (OA) pain is a significant issue among older females, with intervertebral disc (IVD) degeneration (IVDD) and facet joint OA (FJOA) common causes of this condition. The incidence of OA is two-fold greater among women than men, with menopause amplifying this difference.

Estrogen receptors are found in IVD tissues and joints, thus indicating that estrogen may be involved in OA pain. This observation has led researchers to hypothesize that estrogen supplementation could improve lower back and OA pain.

In a recent study published in Bone Research, researchers review existing evidence on the association between estrogen, IVDD, OA, FJOA, and lower back pain (LBP).

Study: Low back pain and osteoarthritis pain: a perspective of estrogen. Image Credit: Sasan Paraksa / Shutterstock.com

Introduction to LBP, OA, IVDD, and FJOA

LBP and OA are significant health and economic burdens for patients, their families, and society. LBP episodes occur in the lumbar area of the vertebral column, which carries the majority of the upper body’s weight.

LBP is primarily caused by IVDD and FJOA. Women are more likely to suffer from LBP than men, with postmenopausal middle-aged females at an increased risk of suffering from LBP than younger females, likely due to hormonal changes such as estrogen reduction with age.

OA is a degenerative condition that worsens over time and ultimately results in persistent discomfort. OA often affects the body's joints, including the spine, hands, hips, and knees.

Women between 50 to 60 years of age have a four-fold greater risk of OA than similarly-aged men. Middle-aged women are also associated with a 10% and 40% greater likelihood of developing OA in the hip and knee joints than their male counterparts, respectively. Several studies have also reported that OA may be more severe in women.

LBP is influenced by various biopsychosocial and lifestyle factors. Older individuals at a greater risk of chronic pain due to reduced IVD viscoelasticity, proteoglycan synthesis, water content, structural integrity, increased oxidative stress, cell death, and senescence with age. FJOA arises due to spinal degeneration and is considered another primary cause of LBP.

Role of estrogen in OA and LBP pain

Estrogen, a steroid hormone released from human ovaries, plays a crucial role in the growth, differentiation, and normal functioning of female reproductive organs, bone health, and musculoskeletal metabolism.

Estrogen promotes bone matrix formation by increasing osteoblastic activity. This hormone can readily penetrate cellular membranes and efficiently bind with estrogen receptors (ERs).

Previous studies have shown that estrogen treatment can increase chondrocyte prostaglandin synthesis, reduce proteoglycan synthesis, and suppress cyclooxygenase-2 (COX-2) expression in cultured rabbit chondrocytes.

Estrogen deficiency may facilitate IVDD through changes in cartilage endplate remodeling and vertebral osteoporosis. In addition to IVDD, estrogen deficiency may also promote FJOA, as demonstrated in ovariectomized (OVX) mice with decreased surface area, thickness, and volume, surface subchondral bone damage, and increased osteoclasts within their subchondral bone.

Estrogen supplementation is associated with anti-inflammatory and anti-hyperalgesic effects on nucleus pulposus cells (NPCs) of IVDs in OVX murine animals with IVDD. Following estradiol (E2) supplementation, arthritic diseases within the lumbar facet joint were prevented, as was cartilage degradation.

Estrogen medication may be beneficial for the treatment of LBP by slowing or inhibiting IVDD. Estrogen levels are directly correlated to joint health and remodeling, with low estrogen levels related to increased articular soft tissue thickness and reduced bone volume among murine animals with osteoarthritis in the temporomandibular joint (TMJ).

E2/progesterone therapy can improve condylar cartilaginous and vertebral disc health, reduce joint inflammation, and diminish joint nociception. Clinical studies have indicated that estrogen supplementation can reduce the frequency of joint pain among postmenopausal females. In fact, estrogen and estrogen-related medicinal drugs have been shown to reduce the incidence and prevalence of hand, hip, and knee OA and lower arthroplasty rates.

How does estrogen alleviate IVDD, OA, and FJOA?

Estrogen inhibition pathways include the nuclear factor kappa B (NF-κB) and ER-substance P signaling pathways. Estrogen activation pathways include the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, ERα-AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, ERβ-p38 MAPK pathway, and ERα mitogen-activated protein kinase-extracellular signal-regulated kinase (MEK-ERK) pathways.

Estrogen inhibition pathways increase collagen (Col)-I and II and aggrecan synthesis, thereby increasing NPCs and annulus fibrosus cells (AFCs) to reduce IVDD and lower LBP ultimately. Estrogen activation pathways increase cartilage endplate cells (CEPCs) by lowering MMP levels, which are increased in LBP. Estrogen activation pathways may also improve OA by increasing mitophagy and chondrocyte counts.

Conclusions

Estrogen has a crucial role in the health of IVDs, joints, and other tissues that are implicated in OA and LBP. These findings support future studies on estrogen treatment for preventing and managing OA and LBP, particularly during times of low estrogen levels, such as the post-menopausal period.

Nevertheless, additional research is needed to understand better the biological pathways associated with estrogen-induced reductions in OA and LBP pain and the possible negative impacts of estrogen treatment. Future studies must also identify the optimal type of estrogen therapy and dosage to maximize the benefits of this hormone supplementation for diverse pain disorders.

Journal reference:
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.

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Comments

  1. Hannan Ahmad Hannan Ahmad Islamic Republic of Pakistan says:

    This article provides a fascinating exploration of the intricate relationship between estrogen and its potential impact on osteoarthritis (OA) and lower back pain (LBP). As a healthcare professional with a keen interest in musculoskeletal health, I find the insights presented here both enlightening and promising. The presence of estrogen receptors in intervertebral disc tissues and joints underscores the intriguing possibility that estrogen could play a significant role in alleviating pain and preserving joint health, particularly in women who are disproportionately affected by these conditions.

    The gender disparities highlighted, with women facing a higher risk of OA and LBP, emphasize the importance of delving deeper into the mechanisms by which estrogen influences these conditions. Estrogen's effects on bone health, cartilage synthesis, and anti-inflammatory properties, as outlined in this article, offer a compelling rationale for further research into estrogen supplementation as a potential therapeutic avenue. However, it is essential to exercise caution and conduct rigorous studies to better understand the potential benefits and risks associated with estrogen treatment. Identifying the most suitable types and dosages of estrogen therapy for different pain disorders and patient profiles will be crucial in translating these findings into effective clinical strategies. Overall, this article serves as a thought-provoking catalyst for future research in the pursuit of improved treatments for OA and LBP, particularly in populations where estrogen levels may fluctuate, such as post-menopausal individuals.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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