Osteoporosis

Introduction
Osteoporosis is a condition characterised by loss of bone. Bone is comprised of calcium and phosphate and other minerals, structural proteins like collagen and biologically active chemicals or cytokines. Osteoporosis is the loss of minerals and structural proteins ultimately resulting in weakened bone and a tendency to fracture principally the hip and spine but other bones as well like the wrist and humeral neck. This condition occurs typically in both sexes with age but affects woman more commonly (though not exclusively) . Men do get osteoporosis as well however but at an older age compared to women. In principle, the lack of sex hormones as with menopause (andropause in men) predisposes to the development of osteoporosis. In addition however, chronic smoking, alcohol intake and sedentary lifestyles all contribute to the development of osteoporosis. Certain drugs like steroids do cause osteoporosis but this is an uncommon occurrence specifically related to drug therapy.

Epidemiology
With its association with an aging population the condition is set to be one of the largest group of ailments to affect society (Figure 1). Aging women represent the prototype of our understanding of the condition and so most data is available about post-menopausal osteoporosis (PMO). It affects 4% of women between 50-59 years of age, 8% between 60 and 69 years, 25% between 70-79 years and 48% at 80 years and above. This predisposes to fractures of wrist, hip, spine, others. Fractures of the hip and spine, particularly the former can be fatal in the short term as patients affected by these fractures become immobile and unable to care for themselves. In Singapore, the incidence of hip fracture has increased 1.5 times in men and 5 times in women since the sixties. Age-adjusted rates among women over the age of 50 years are currently among the highest in Asia, and approaching those of the West.

Risks of osteoporosis
The consequences of ostoporosis-related fractures is severe:
  • Hip fractures
    • The mortality rate one year post fragility hip fracture is approximately 20% to 27%.
    • Of the 73-80% survivors
      • 20% become semi or fully dependent
      • 39% experience reduced mobility status
      • 8% are cared for by chronic health care facilities in 1994 and has increased to 26% in 2002
  • Vertebral fractures 
    • Cause significant complications including chronic back pain, height loss, kyphosis and limitation of activity
    • There is also an association with increased mortality

Figure 1. The combined case load of osteoporotic fractures is greater than the combined case load of strokes, heart attacks and breast cancer combined (!) 

Who Needs Pharmacologic Therapy ?
There can be some confusion about the indications for use of osteoporosis related medications as there are terms used like "prophylaxis" and "treatment". In the past the idea of "prophylaxis" in osteoporosis was construed as a means of providing the treatment before  osteoporosis occured. This concept has largely been abandoned. Presently therefore , osteoporosis is "treated" with the intention to prevent fractures and the principle guidelines for these are:

  1. Those patients with a history of a fracture of the hip or spine 
  2. Patients without a history of fractures but with a T-score of -2.5 or lower 
  3. Patients with a T-score between -1.0 and -2.5 if FRAX computed 10-year major osteoporosis related fracture probability is at 20% or more or hip fracture probability is at 3% or more (Figure 2)
  4. Rapid rate of change of 3% or more in BMD - this requires repeated scans


Figure 2. The WHO Fracture Risk Assessment Tool (FRAX) is an online tool that can aid in the recommendation for therapy especially in borderline osteoporosis cases with T-score of -1.0 to -2.5

Mechanism of action of common osteoporotic drugs
Most drugs prevent the progression of osteoporosis by inhibiting bone resorption as the body continues to lay down bone (Figure 3). Teriparatide (and maybe Strontium Ranelate) can actually promote bone formation. The widest spectrum of coverage is only provided by estrogen, some bisphosphonates and denosumab.


Figure 3. Mechanism of action of the major classes of osteoporosis related drugs. Most such drugs work by preventing bone resorption.

Drugs used in the treatment of Osteoporosis
Over the last 20 years the list of drugs used in the treatment of osteoporosis has changed dramatically. The heavily contested group of drugs in the bisphosphonate class are the largest single group. Nevertheless it should be understood that while all bisphosphonates probable treat osteoporosis, in general physicians will err towards FDA or national guideline approved drugs. We here present the drugs listed by the AACE (American Association of Clinical Endocrinologists) Post-Menopausal Osteoporosis Guidelines 2015.


The FDA-Approved Medications for treatment of post-menopausal osteoporosis (PMO) are:
                1. Estrogen
                2. Calcitonin 
                3. Alendronate 
                4. Risedronate 
                5. Ibandronate 
                6. Zoledronic acid 
                7. Raloxifene 
                8. Denosumab 
                9. Teriparatide
Fracture risk reduction
This list shows that while all the drugs listed are FDA approved, the do not all have the same spectrum of coverage. In fact it should be evident that only estrogen, alendronate, risedronate, zoledronic acid and denosumab  are able to reduce the risk of spine, hip and non-vertebral fractures.

Fracture risk reduction in PMO

Spine

Hip

Non-vertebral

Estrogen

Yes

Yes

Yes

Calcitonin

Yes

Alendronate

Yes

Yes

Yes

Risedronate

Yes

Yes

Yes

Ibandronate

Yes

Zoledronic acid

Yes

Yes

Yes

Raloxifene

Yes

Denosumab

Yes

Yes

Yes

Teriparatide

Yes

Yes


Conclusion and recommendations
We have presented here a succinct recommendation on treatment of osteoporosis.  We hope that it will aid in the selection of the treatment regime most appropriate for you.