Protective Effect of Estrogen

On Bone Mineral Density.

Dr Umair Abu Bakar Siddiq
Dr Sheikh Suffyan Zahid

1st Sept 2023

Bone Structure
Periosteum
•Membrane
•Covers outer surface of bones
•Blood vessels
•Sensory nerves

Cortical bone
•Compact bone
•Hard, exterior bone
Trabecular bone
• Cancellous bone or Spongy bone
• Soft, flexible
• Found at ends of long bones
• Trabeculated
• Lots of surface area

Medullary cavity
•Contains marrow
Bone Cells
Osteoblasts
•Synthesize bone matrix

Osteoclasts
•Specialized macrophages
•Derived from circulating monocytes
•Secrete acid (H+) and proteases
•Dissolve bone matrix
Bone Turnover

• Balance between formation/breakdown

• Modulated by signals from osteoblasts
• Some stimulate osteoclasts (RANK-L)
• Some limit osteoclasts (OPG)
• Combination determines formation/breakdown
RANK
•Receptor activating nuclear factor kB
•Receptor expressed on surface of osteoclasts
•Ligand binds to receptor
•Osteoclast stimulation
RANK-L
•Receptor activating nuclear factor kB ligand
•Binds RANK
•Expressed by osteoblasts
Osteoprotegerin (OPG)
•Decoy receptor for RANK-L
•Binds RANK-L
•Prevents RANK-L from binding RANK
•Made by osteoblasts

M-CSF
•Macrophage colony stimulating factor
•Secreted by osteoblasts
•Stimulates osteoclasts
Osteoporosis
•Porous bone due to a decrease in bone mass
•Weak bones prone to fracture
Trabecular bone > cortical bone
• High trabecular bone content:
- Spine (Compression Fractures)
- Head of femur (hip)
- Wrist (Colles’ Fracture)
Bone Mass
•Peak bone mass occurs in young adulthood
•Many influences: gender, genetics, diet
•Decreases slowly thereafter
Menopause
• Accelerates bone loss in women
• Caused by estrogen deficiency

Estrogens
• Induce apoptosis of osteoclasts
• Stimulate OPG synthesis by osteoblasts
- More OPG -> Less osteoclast activity
• Decrease M-CSF and RANK production
DEXA Scan
Dual-energy X-ray absorptiometry
• Two X-rays of different energy levels aimed at bones
• T score: patient BMD vs. healthy 30-year-old BMD
• Normal: -1.0 or higher (least fractures)
• Osteopenia: - 1.0 to - 2.5
• Osteoporosis: -2.5 or lower
• Recommended for screening in women >65
Osteoporosis Treatment Modalities
• All patients: lifestyle modification
• Weight-bearing exercise
• Avoidance of heavy alcohol use
• Smoking cessation
• Calcium and vitamin D supplementation
- Bisphosphonates (first line of treatment)
- Raloxifene:
• SERM (Selective Estrogen Receptor Modulator)
• Estrogen actions on bone
• Anti-estrogen in breast/uterus
• Also used for prevention of breast cancer
Thank you.