Osteoporosis, OP


## Basic introduction

  • OP is commonly defined as a disease that is characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture riskb


  • OP is a skeletal disorder that is characterized by compromised bone strength predisposing a person to an increased risk of fracture (definition by NIH Consensus Development Panel)b.

## Types of OP

  • OP is broadly classified into primary and secondary OP
  • Primary OP (Type 1 and Type 2) is due to the classical age-related loss of bone from the skeleton while the secondary OP (Type 3) is due to other diseases / conditions that predispose to bone loss.
  • Type 1 OP refers to postmenopausal OP
  • Type 2 OP refers to senile OP that occurs in both women and men > 70 yrs

## Risk factors for OP

  • Age (increases with age)
  • Gender (more common in females)
  • Obesity (more prevalent in obese)
  • Smoking (more common in smokers)
  • Diet (deficiency in calcium, vitamin D and general balanced diet)
  • Past history of fracture
  • Caucasian race
  • Poor general health
  • Dementia
  • Impaired vision
  • Inadequate physical activity
  • Alcoholism
  • Caffeine consumption
  • Estrogen deficiency
  • Low body weight
  • Kidney stone disease
  • Use of corticosteroids
  • Treatment with aromatase inhibitors such as anastrozole, letrozole and exemestane (in females)
  • Androgen deprivation therapy (or androgen suppression therapy) such as cyproterone acetate, flutamide and bicalutamide,

## WHO criteria for clinical diagnosis of OPa, b

  • The T-score is the number of standard deviations of the Bone Mineral Density (BMD) measurement above or below that of young healthy adults of the same sex
  • BM) values b:

T-score ≥ -1:  Normal

-1 > T-score > -2.5: Low bone mass

T-score ≤ -2.5:  OP

T-score ≤ -2.5 plus fracture: Severe OP

## Statistics

  • Number of postmenopausal Caucasian women with OP at the hip, lumbar spine or distal forearm: 30%c
  • Number of fractures globally that are caused by OP: 9 million (50% of this occurring in the Americas and Europe)d
  • The estimated lifetime risk for a wrist, hip or vertebral fracture in developed countries: 30-40% d
  • Prevalence of osteoporosis in Kenya: 24.3%e
  • Prevalence of osteopenia in Kenya: 32%e
  • Mortality rate after OP: 1.6 fold following vertebral fracture and 6 fold following hip fracturef
  • Rate of bone loss after 40 yrs.: 0.3 - 0.5%/yr
  • Rate of bone loss after menopause in women: ≈ 3 - 5%/yr for 5-7 yr (10 times increase)
  • Sometimes OP is called a “silent disease” as it is often asymptomatic
  • It mainly presents as a sudden fracture
  • Polyarthralgia
  • Lower back pain
  • Loss of height over time
  • A stooped posture
  • Dual-energy X-ray absorptiometry (DXA) to measure Bone Mineral Density (BMD)
  • Normal X-ray
  • Serum levels of calcium, 25-OH vitamin D, albumin, creatinine, phosphate, parathyroid hormone, alkaline phosphatase and testosterone
  • Thyroid function tests
  • Urinary free cortisol
  • Osteomalacia
  • Vitamin D deficiency (mostly accompanied by osteomalacia)
  • Multiple myeloma
  • Metastatic bone malignancy
  • Primary hyperparathyroidism
  • Multiple myeloma
  • Chronic kidney disease-bone and mineral disorders
  • Scurvy
  • Idiopathic transient osteoporosis of hip

## Differentiating osteoporosis and osteomalacia

  • Both diseases decrease bone mass (i.e. they cause osteopenia)
  • Osteomalacia is mainly caused by the impaired mineralization as a result of severe vitamin D deficiency or its abnormal metabolism while osteoporosis is mainly due to a combination of low peak bone mass, increased bone resorption, and decreased osteogenesis
  • In osteomalacia the ratio of bone mineral: bone matrix is low (as the disease involves the loss of minerals more than other components of bones) while in osteoporosis the ratio of bone mineral: bone matrix is normal (as all components are lost in approximately equal measure)
  • Mitigation of the above risk factors (e.g. balanced diet, adequate body activity, cessation of smoking and alcohol intake, and safe environment)
  • Prevention of fall

1. Kanis, J. A., Melton, L. J., Christiansen, C., Johnston, C. C., & Khaltaev, N. (1994). The diagnosis of osteoporosis. Journal of bone and mineral research, 9(8), 1137-1141. Chicago\

2. Szulc, P., & Bouxsein, M. L. (2011). Overview of osteoporosis: epidemiology and clinical management. Vertebral fracture initiative resource document.

3. Melton, J. L. (1995). Perspectives: how many women have osteoporosis now? Journal of Bone and Mineral Research, 10(2), 175-177.

4. Kanis, J. A., Johnell, O., Oden, A., Sernbo, I., Redlund-Johnell, I., Dawson, A., ... & Jonsson, B. (2000). Long-term risk of osteoporotic fracture in Malmö. Osteoporosis international, 11(8), 669-674.

5. Odawa, F., Ojwang, S., & Muia, N. (2004). The prevalence of postmenopausal osteoporosis in black Kenyan women. J. Obst. Gyn. Eastern and Central Afr, 17(suppl 1), 45-46.

6. Panula, J., Pihlajamäki, H., Mattila, V. M., Jaatinen, P., Vahlberg, T., Aarnio, P., & Kivelä, S. L. (2011). Mortality and cause of death in hip fracture patients aged 65 or older-a population-based study. BMC musculoskeletal disorders, 12(1), 105.

Freitag, A., & Barzel, U. S. (2002). Differential diagnosis of osteoporosis. Gerontology, 48(2), 98-102


## Life-style modification

  • See under the “Risk factors” and “Prevention” of this disease

## Bisphosphonates

  • They are the first-line of pharmacotherapy
  • They include alendronate, ibandronate, and zoledronic acid
  • Alendronate: Osteoporosis in postmenopausal women: 10mg OD. Prevention of osteoporosis in postmenopausal women: 5mg OD. Paget's disease of bone: 40mg OD x 6/12.


  • Ibandronate: Orally: 50mg OD. Inf: 6 mg IV given every 3-4 weeks. The dose should be infused over 1hr


  • Zoledronic acid: Prevention of skeletal related events [pathological fractures, spinal compression, radiation or surgery to bone, or tumor-induced hypercalcemia] in patients w/ advanced malignancies involving bone. Recommended dose: 4 mg [diluted with 100ml NaCl 0.9% w/v or glucose 5% w/v soln] given as a 15-min IV infusion every 3-4 wk. Reduce dose in patients with preexisting mild to moderate renal impairment. Treatment of hypercalcemia of malignancy (HCM): Recommended dose - 4 mg given as a single 15-min IV infusion. No dose adjustment in patients with mild to moderate renal impairment. Without hypercalcemia 500 mg oral Ca supplement and 400 IU vitamin D daily.

## Estrogen Receptor Modulators

  • They are the 2nd-line of pharmacotherapy in postmenopausal women
  • Raloxifene: Prophylaxis and treatment of osteoporosis: Tabs 60mg OD [without regard to meals].

## Drugs that increase bone formation

  • Strontium Ranelate (a reserve drug that is to be used only when other drugs are not effective): 1 sachet diluted in half a glass of water taken once daily.

## Calcium and vitamin D supplementation

  • Calcium: 1200 -1500 mg of calcium daily either through supplementation or  diet such as milk (where a glass of milk contains about 300 mg of calcium)
  • Vitamin D: Adults < 50yrs: 400-800 IU daily; >50yrs, 800 - 1,000 IU daily

## Other treatments

  • Testosterone (in cases of low testosterone levels in men with OP)
  • Hormone replacement therapy (HRT) and estrogen replacement therapy (ERT)
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