Rheumatology‎ > ‎

Osteoporosis

OSTEOPENIA

WHO Fracture Risk Assessment Tool 
69 yo F is seen for Osteopenia. Patient has a history of breast cancer treated 3 years back. ER, PR status is not known. How should you treat this patient along with Ca, and Vitamin D supplementation to prevent Osteoporosis (FRAX score is > 5 for Hip fracture and 12 for Major Fracture). 

1. Start Ibandronate (Boniva)
2. Start Denosumab (Prolia) 60 mg) is administered by subcutaneous injection once every six months
3. Start Raloxifen (Evista).
4. Start Alendronate (fosamax). 
5. Start Teriperatide (Forteo) dose of PTH 1-34 is 20 mcg/day. A multi-dose prefilled pen (containing 28 doses) is available. It is administered via subcutaneous injection into the thigh or abdominal wall. The initial dose should be administered in a setting where the patient can sit or lay flat, if symptoms of orthostatic hypotension occur. Due to the potential risk of carcinogenicity, PTH treatment should be given for a maximum of two years
6. Start Risedronate (actonel) 

Ans: Given history of Breast cancer, Raloxifen is useful for the prevention of invasive breast cancer. 

Note: Vitamin Supplementation of 400-800 IU/day leads to appropriate level of vitamin D, even as much as near 70. 

Osteoporosis/Bone Disease

Mechanisms of Anabolic Therapies for Osteoporosis NEJM 2007


Bisphosphonates for the prevention and treatment of osteoporosis BMJ 2015

Summary 
1.5 M fractures / yr in US
Disease is characterized by Skeletal fragility and micro architectural deterioration. 
300K hip fractures / yr in US 
40 mil women with low BMD
Hip and Spine Fractures: Increased risk of death 
Overview
Goal: Prevention of future fractures
Try to define absolute risk for an individual 
Identify high risk patients including prior fractures, 
DM itself is a risk for osteoporosis
Smoking: Linked to low BMD
Excess Alcohol: Linked to increased risk of fall 

Ca and Vit D: Efficacy is controversial 
Daily supplementation and not intermittent supplementation may have modest reduction of fall 
Ca: 1-1.5 g / day
Vit D : 600-800 IU / day 
 

Drugs: 2 main mechanism of action 
  • Anti-resorptive : 5 classes of medications have antiresorptive properties 
    • Bisphosphonates
    • Denosumab (Prolia)
    • Estrogen 
    • SERM
  • Anabolic : 
    • Teriperatide
    • Romosozumab
3 Medications have only vertebral fracture risk reduction
  • Ibandronate
  • SERM (Raloxifene)
  • Calcitonin
1 medication has Vertebral, Non-vertebral fracture reduction BUT HIP is NOT Defined
  • Teriperatide
  • Question
    • 95 yo M patient with Pagets disease has ORIF after R Hip fracture. What do you give for the treatment?
      • 1. Teriperatide
      • 2. Alendronate
        • Answer: Alendronate. 
        • Teriperatide is wrong choice for 2 reasons.
          • 1. It is an anabolic drug with risk of osteosarcoma especially in patients with Pagets disease. 
          • 2. There is no Data of use of Teriperatide when used for prevention of Hip Fracture. 
REST  has vertebral, Non-vertebral, and HIP fracture reduction 

3 Medication are used for prevention
  • Bisphosphonates
  • SERM
  • Estrogen 

Postmenopausal Osteoporosis NEJM 2016

For prevention of GIO, only 2 bisphosphonates are used. Risedronate, and Zoledronic Acid. 
For treatment of osteoporosis in MEN, Ibandronate is NOT used
For recurrent fracture, only Zoledronic acid is used. 

Controversies: Questions of concern from table below compared to NEJM table above. 
Risedronate for Hip Fracture prevention ??
Alendronate for Non-vertebral fracture ??


Bisphosphonates for the prevention and treatment of osteoporosis BMJ 2015


Osteoporosis: now and the future Lancet 2011



52 yo F with Scleroderma, Raynauds, B12 deficiency is seen for chronic back pain. Patient was diagnosed of vertebral compression fracture. Diagnosis of Steroid induced Osteoporosis was made. Patient was on Alendronate for osteoporosis in the past. DEXA results are as below. CXR shows recurrent vertebral fracture. GFR is 25.  
Vitamin D is 15. TSH is normal. What is the best treatment strategy in addition to Ca, Vitamin D supplementation? 
1. Start Ibandronate 
2. Start Denosumab 
3. Test for celiac disease.
4. Treat with Alendronate. 
5. Treat with Teriperatide 
6. 3 and 5 


Note: Ans. 
Teriperatide address the decreased bone formation affect of steroids by decreasing the osteoblast apoptosis. Anti-resorptive medication (bisphosphonate do not have this advantage as they work on osteoclast predominantly). 

Alendronate is not the write answer for it failed to work in the past, but also is not used for recurrent vertebral fracture. 
Ibendronate (only used for PMO). Ibandronate is used in very limited set up. (see above in the table) 

Vitamin D deficiency must be treated before use of Denosumab. Denosumab also does not address decreased bone formation effect of steroids as it acts on osteoclasts. 

Zoledronic acid could be used, however same limitation of anti-resorptive medications in a patient with GIO
Note: 
Alendronate is not used for the prevention of GIO. Risdronate, and Zoledronic acid can be used. 

52 yo F with Scleroderma, Raynauds, B12 deficiency is seen for chronic back pain. Patient is on chronic steroid use. What is the best to prevent osteoporosis.
Ans: Resedronate or Zoledronic acid. Note Ibandronate (Boniva) and Alendronate (fosamax) are not best for prevention of GIO

52 yo F with Scleroderma, Raynauds, B12 deficiency is seen for chronic back pain. Patient is on chronic steroid use. DEXA including hand is done. Shows osteoporosis of wrist. What is the best bisphonate to treat osteoporosis.
Ans: Resedronate or Zoledronic acid. Note. Like in case of GIO prevention Ibandronate (Boniva) and Alendronate (fosamax) are not best for treatment of non-vertebral osteoporosis.

52 yo F with Scleroderma, Raynauds, B12 deficiency is seen for chronic back pain. Patient is on chronic steroid use. DEXA including hand is done. Shows osteoporosis of wrist and hip. What is the best bisphonate to treat osteoporosis.
Ans: Zoledronic acid. Note. Like in case of GIO prevention Ibandronate (Boniva) and Alendronate (fosamax) are not best for treatment of non-vertebral osteoporosis. While if it was osteoporosis of Wrist only, Risedronate could have been used, however, is not best for Hip Osteoporosis. Hence, only option in this case is Zoledronic acid.
Of-course Teriperatide actually helps counteract the pathogenesis of steroid on bones. 








Note: 
On treatment, if BMD T score decreases from -2.5 to -3.5, risk of fracture is doubled. On the contrary, on treatment, if BMP improves to -2.5 from -3.5, the decrease in fracture risk not only by 50 % but much more. Even as low as 0.1 improvement in BMD in wrist will lead to decrease fracture by around 50 %. 

12 million 50 yr or older has osteoporosis
1 in 2 women will have life time OP fracture (25 % spine, 15 % hip) 
1 in 5 min will have osteoporotic fractures 
Racial differences
  • Whites have higher incidence
Less than 30% of patients with hip fractures are treated with anti-osteoporsosis medication 

Bone-Density Testing Interval and Transition to oseoporosis in Older Women 
NEJM 2012
  • Moderate osteopenia (-1.5 - -- 2.00: 5 yrs
  • Severe osteopenia (-2 - -2.5): 1 yr 
  • However, this analysis did not capture the spinal osteoporosis. 
  • JAMA 2012
    • Mild osteopenia and low frax: 5-10 yr
    • Advanced osteopenia and high frax: every 2 yr
When should DEXA be repeated?
  • Controversial and unclear 
  • 1-3 yrs of therapy
  • Stay the same or slight improvement is an excellent report
  • And, when drug holiday is to be considered
What should DXA report include?
  • Manufacturar: Hologic, Lunar, Norland. Important that the same machine be used subsequent dexa scan. 
  • Images of regions of interest.
What testing should an internist obtain in a patient with newly diagnosed Low BM Density?
  • Yes: Calcium, Albumin, Mag, Phosphorous, PTH, 25 OHVit D, ALP, BUN/Cr, TSH 
    • BMD cannot differentiate osteomalacia vs osteoporosis as in hypophosphotemia, in which case no need of osteoporotic medication. Correct Phosphorous
  • Possibly: Ur Proteinuria assessment, Celiac Disease, MM, Hypogonadism, Urinary Cortisol
Medicaton associated with increased risk of osteoporosis fracture
  • Steroids, Cyclosporin, Tacrolimus, GNRH agonists, Depo-medroxyprogesterone (No estrogen leads to bone loss), Aromatase inhibitors, Tamoxifen (premenopausal women), Anticonvulsants
  • Unclear if inhaled steroids cause it. Some reports say yes, others say no. 
  • PPI, TZD, Anti-convulsants, 
Who should be treated?
  • Prior vertebral (clinical or morphometric - seen in imaging but not clinically - increased 4-5 risk of future fractures), hip, pelvic, humeral, and forearm fragility fracture (irrespective of T score). Falling from standing heights. 
Treatment options
  • 1-1.2 gm of ca (PTH < 60, or Urinary C 100-200/gm of Cr assuming not on HCTZ)
  • Aim for higher Vitamin D level (per endocrine society guidelines)
Comments