Title: Osteoporosis causes accordian

Peak Bone Mass

Peak bone mass is the amount of bony tissue present at the end of the skeletal maturation.
Factors that influence peak bone mass are as follows:

- Genetically determined
  - driven by sex hormones
  - depends on sites measured (spine, femur, radius)
- Ethnicity
  - occurs later in Chinese American than Caucasians
- Women
  - peak accrual at ages 11-15 years
  - 95% achieved by late teens
- Men
  - peak accrual later teens
  - maximum spine by age of 20 years
  - radius and remus by mid 20s
- Delay / Failure of puberty
  - Primary hypogonadism
    - Turners syndrome
    - Klinefelter syndrome
    - Cryptorchidism
    - Chemotherapy, radiotherapy
    - Chronic systemic diseases
    - Absent cervix / vagina
  - Secondary hypogonadism
    - Kallmann syndrome
    - CNS tumors
    - Malnutrition
    - Chronic systemic illness

Hormones

The primary hormonal cause of osteoporosis is estrogen deficiency (Type I)

- Women:
  - Occurs earlier
  - At menopause, bone loss rates increase by 2-6 fold, and for subsequent 6-8 years
  - Impairs calcium absorption from gut
- Men:
  - Testosterone declines with age
  - Estrogen declines with age (associated with increased fat)
  - Both androgens and estrogen contribute

Generic Based Factors

There is association between low bone mass density and fracture, and gene polymorphisms (single base changes).

- Vitamin D receptor
- Insulin-like growth factor (IGF-I) - CA repeat in promoter region
- Estrogen receptor
- Low density lipoprotein receptor-related protein 5 (LRP5)
- Interleukin 6 (IL6)
- Osteoprotegerin (OPG)

Genetic linkage is a gene hunting technique that traces patterns of heredity in large, high-risk families. It looks for inherited DNA markers (e.g. sequence repeats) in diseased family members and identifies chromosome regions and potential disease gene by sequencing.

Chromosome 20p12

- Identified as a significant linkage signal to osteoporosis risk.
- Identified bone morphogenetic protein-2 (BMP-2)
- Confirmed a Ser to Ala polymorphism

Age

Osteoporosis Type II or senile is age related.

As age increases, the incidence of osteoposis and fractures increases.

Cell-Based Factors

When the bone remodeling balance is disrupted in favour of osteoclast function, bone loss will result. (osteoclast activity > osteoblast activity)

Additionally, osteoporosis can occur when stem cells begin to favour differentitation to adipocytes (fat formation) instead of osteoblasts (bone formation). In this scenario, fat is being formed instead of new bone, resulting in lower bone mass and fragility.

Secondary Causes

There are many secondary causes that can lead to (secondary) osteoporosis, here are just a few:

- Genetic factors
- Hypogonadal states
- Endocrine disorders
- Gastrointestincal disorders
- Hematological disorders
- Rheumatic and autoimmune diseases
- Miscellaneous conditions and disease

Medications (e.g. Glucocortocoids)

Many medications can result in reduced bone mass and therefore osteoporosis:

- Anticoagulants
- Anticonvulsants
- Aromatase inhibitors
- Barbiturates
- Cancer chemotherapeutic drugs
- Cyclosporin A
- Glucocorticoids
- Gonadotropin-releasing hormone agonists
- Lithium
- Depot-medroxyprogesterone acetate

Glucocorticoid Induced Osteoporosis

- the most common form of secondary osteoporosis
- due to long term use of oral glucocorticoids (>3 months)
- results in decreases osteoblat activity and increased osteoclast activity
- results in increased calcium excretion and decreased calcium absorption