Ask Your Question - Osteoporosis

1. What is the role of One-Alpha® treatment in Osteoporosis?
Part of the pathogenesis of Osteoporosis is: * Poor calcium absorption from the intestine * Declining renal function due to age

2. What are the differences between One-Alpha® & plain Vit. D or a multi-vitamin containing Vit. D?
See Table

3. What about Calcium supplement with One-Alpha® treatment?
If the patients dietary intake contains calcium then Calcium supplement is not a must.

4. What about the equivalence of One-Alpha® microgrammes and Vit. D International Units?
There is no Relation and it is like if you want to convert Litres into Kilogrammes.

5. When is the bone pain relieved?
Bone pain in Osteoporosis is a result of bone resoprtion. Once bone resorption is corrected, bone pain is relieved.

6. Can I use One-Alpha® with liver impaired patients?
Yes, The fact that One-Alpha® requires a 25 hydroxilation in the liver leads to speculations about its activity in the presence of liver disorders.

7. What are the possible side effects from the use of One-Alpha®? / Are there any allergies or hypersensitivity with One-Alpha® treatment?
The only side is Hypercalcaemia and it is avoided by regular monitoring of the patient serum calcium during treatment (every 3 months).

8. Can I combine One-Alpha® with calcitonin?
Yes, Calcitonin will: * Inhibit bone resorption * and have a remarkable analgesic effect.

9. Can I combine One-Alpha® with Hormonal Replacement Therapy (HRT)?
Yes, Estrogen will: delay or prevent bone loss.

10. What are the differences and advantages of alfacalcidol versus plain vitamin D?
Plain vitamin D will only show effects on calcium metabolism and bone mineral density in patients with preexisting vitamin D deficiency. Alfacalcidol is hydroxylated in the liver to 1,25-dihydroxycholecalciferol, the highly active D-hormone, with specific effects on the gut, bone, parathyroid glands, and several other tissues.

11. What is the rationale of using alfacalcidol in corticosteroid-induced, senile, post-transplantation, and postmenopausal osteoporosis?
Alfacalcidol increases intestinal calcium absorption, reduces hyperactivity of parathyroid glands, decreases bone resorption, and stimulates osteoblastic bone formation. Accordingly beneficial effects have been reported in all mentioned types of osteoporosis.

12. Are there clinically relevant differences between alfacalcidol and calcitriol?
Pharmacodynamic difference: After oral ingestion calcitriol will partly bind directly to specific receptors of the intestinal mucosa and increase calcium absorption. Alfacalcidol is absorbed by intestinal cells and transported by the portal system to the liver. Only after hepatic 25-hydroxylation will it exert its hormonal effects.

13. What are the mechansims for the fracture reducing potency of alfacalcidol?
Although large studies are still lakcing there is accumulated evidence today that long-term treatment with alfacalcidol is able to significantly reduce the rate of new vertebral fractures. The contributing mechanisms are inhibition of bone resorption, stimulation of osteoblasts, and increase in muscle strength.

14. How safe is alfacalcidol during long-term therapy?
No toxic or teratogenic side effects have been reported for the vitamin D analogue alfacalcidol. There is a moderately augmented risk for hypercalciuria and a very low risk for hypercalcaemia. These risks may increase with the amount of oral calcium intake.

15. Combination of alfacalcidol with other drugs?
Different combinations are possible (HRT, raloxifen, calcitonin, fluoride, bishopsphonates), but only small pilot studies have been carried out so far. Preliminary results are encouraging.

16. Prevention and treatment of secondary hyper-parathyroidism in chronic renal insufficiency?
Alfacalcidol plus calcium carbonate is an approved treatment to increase lowered serum calcium, to reduce secondary hyperparathyroidism and the risk of renal bone disease in patients with chronic renal failure.

17. What is the therapeutic classification?
Vitamin D and analogues.

18. Can One-Alpha® be used in patients with reduced liver function?
The active metabolite of vitamin D is 1,25(OH)2D3 (calcitriol). So, as One-Alpha® is only hydroxylated in the 1-position, it requires activation through 25-hydroxylation, which takes place in the liver.

19. What is the equivalence in international units between One-Alpha® and plain Vitamin D?
Previously the concentration of plain vitamin D was tested in an animal model. The strength of the concentration was measured in international units (IU). Today, the strength is measured in mcg.

20. What is the bioequivalence of One-Alpha® and calcitriol?
In its guidelines for defined daily dosis (DDD) the WHO states that DDD for alfacalcidol and calcitriol is 1 mcg for both drugs, saying that the bioequivalence is 1:1.

21. What is the DDD for One-Alpha® and Calcitriol?
The DDD for One-Alpha® as well as calcitriol is 1mcg.

22. Can One-Alpha® injection be added to infusion fluids?
It is not recommended to add One-Alpha® injection to an infusion fluid. One-Alpha® injection should always be given in a shunt as close as possible to patients, as it is done in haemodialysis patients, because of the risk of absorption of One-Alpha® by plastic.

23. Can One-Alpha® injection be diluted?
It is possible to dilute the One-Alpha® injection in a mixture of propylenglycol and isotonic NaCI 1:1.

24. Does One-Alpha® relieve bone pain in patients with osteoporosis?
Several studies have shown that alfacalcidol reduces the bone pain in osteoporotic patients.

25. What are the main causes of secondary hyperparathyroidism?
It is well accepted that the main factor leading to the development of secondary hyperparathyroidism is hypocalcaemia.

26. Can One-Alpha® be taken safely with Ca channel blockers of antihypertensive drugs?
Yes it is safe. One-Alpha® is safely administered with Calcium channel blockers and antihypertensive drugs.

27. What is the rationale use of Calcium with Vitamin D supplement in the treatment of Osteoporosis?
Of course it is possible to administer One-Alpha® alone, without Calcium.

28. What would be the optimum dose for One-Alpha® in nursing home elderly patients?
Recent studies involving more than 5000 elderly patients resident in nursing homes demonstrated that a daily dose of One-Alpha® 1 mcg plus 500 grams of calcium ensured optimal functional mobility and reduced the frequency of falls in those patients.

29. What is the optimal dose of One-Alpha for postmenopausal osteoporosis for a patient who is taking: 1000 mg calcium daily Fosamax 70 mg once weekly, and would like to add One-Alpha® (alfacalcidol)?
The optimal dose of One-Alpha® is 1 microgram for postmenopausal osteoporosis, ...

30. I am a case of Idiopathic Hypoparathyroidism. I am taking 1 mcg of one alpha with calcium supplements. When calcium level rises then calcium supplementation is reduced....
I am a case of Idiopathic Hypoparathyroidism. I am taking 1 mcg of one alpha with calcium supplements.When calcium level rises then calcium supplementation is reduced. Should my dose of one alpha be reduced or what shoud be the optimum blood levels of 25 OHD to be maintained to avoid overdosage of One-Alpha®. Secondly, should one alpha be taken in single dose or two 12 hourly divided doses.

31. What is osteoporosis? How does it occur? What is its mechanism?
Osteoporosis, which literally means "porous bone", is a disease in which the density and quality of bone are reduced.

32. Which one is best, Alfacalcidol or Calcitriol for the treatment of Osteoporosis?
See table below...

33. Is there relation between vitamin D deficiency and Urolithiasis for female in menopausa?
Patients with low vitamin D supply tend to have low normal serum calcium and a low renal calcium excretion.

34. What would be the best medication for females in menopause with history of kidney stone, and chronic back pain in right costo-vertebral angle.
Bone densitometry should be performed to prove whether the back pain is related to osteopenia or osteoporosis. An x-ray of the spine could show degenerative changes or fractures.

QUESTION
1. What is the role of One-Alpha® treatment in Osteoporosis?
 
ANSWER

Part of the pathogenesis of Osteoporosis is:
* Poor calcium absorption from the intestine
* Declining renal function due to age

Plain form of vitamin D requires liver and kidney hydroxylations to become activated form of Vitamin D.

One-Alpha® does not require kidney activation but only liver activation.

Therefore, One-Alpha® will correct the state of calcium malabsorption from the intestine and increase the bone mineral density in osteoporosis.
Without the need of kidney activation.

QUESTION
2. What are the differences between One-Alpha® & plain Vit. D or a multi-vitamin containing Vit. D?
 
ANSWER
 

One-Alpha® 0.5μg daily is more effective and easier to control than plain Vit. D.

QUESTION
3. What about Calcium supplement with One-Alpha® treatment?
 
ANSWER

If the patients dietary intake contains calcium then Calcium supplement is not a must.

Combine:
One-Alpha® μg daily and Calcium
                  OR
use One-Alpha® alone if patient daily calcium supplement is ensured.

QUESTION
4. What about the equivalence of One-Alpha® microgrammes and Vit. D International Units?
 
ANSWER

There is no Relation and it is like if you want to convert Litres into Kilogrammes.

QUESTION
5. When is the bone pain relieved?
 
ANSWER

Bone pain in Osteoporosis is a result of bone resoprtion. Once bone resorption is corrected, bone pain is relieved.

If One-Alpha® is given alone it could be established that bone pain will be relieved with 2-3 months.

QUESTION
6. Can I use One-Alpha® with liver impaired patients?
 
ANSWER

Yes,
The fact that One-Alpha® requires a 25 hydroxilation in the liver leads to speculations about its activity in the presence of liver disorders.

"However the clinical efficacy of small doses of One-Alpha® in patients with primary biliary cirrhosis implies that there is no defect in the hydroxylation step even in the presence of severe liver disease". (1), (2)

 

REFERENCES
1. Compston JE, Crowe JP, Horton LWL
Treatment of osteomalacia associated with primary biliary cirrhosis with oral 1-alpha-hydroxy vitamin D3.
Br Med J 1979; 2: 309

2. Varghese Z et al.
The effect of oral 1-alpha-hydroxyvitamin D3 and 1,25-(OH)2D3 on the intestinal absorption of calcium and phosphate in primary biliary cirrhosis.
Vitamin D Basic Research and its Clinical Application 1979; 1045-1049.
Ed: AW Normal et al. Walter de Gruyter, Berlin.

QUESTION
7. What are the possible side effects from the use of One-Alpha®? / Are there any allergies or hypersensitivity with One-Alpha® treatment?
 
ANSWER

The only side is Hypercalcaemia and it is avoided by regular monitoring of the patient serum calcium during treatment (every 3 months).

QUESTION
8. Can I combine One-Alpha® with calcitonin?
 
ANSWER

Yes,
Calcitonin will:
* Inhibit bone resorption
* and have a remarkable analgesic effect.

While One-Alpha® will:
* Improve intestinal calcium absorption
* Increase bone mineral content.

Thus a combination of:
"Calcitonin and low doses of 0.5-1μg of 1α(OH)D3 or 0.025-0.5μg 1,25(OH)2D3 will prove to be an effective therapy in the treatment of Osteoporosis". (3)

 

REFERENCES
3. In: Osteoporosis Eds: G Menczel, et al. Chichester: John Wiley & Sons, 1982: 394-406

QUESTION
9. Can I combine One-Alpha® with Hormonal Replacement Therapy (HRT)?
 
ANSWER

Yes,
Estrogen will: delay or prevent bone loss.

But as Calcium malabsorption and impaired Kidney functions are important features of osteoporosis, Estrogen will be of little value.

While One-Alpha® will:
* Improve intestinal calcium absorption
* Increase bone mineral content.

Combine:
One-Alpha® 0.5μg daily and HRT
"A much more pronounced bone sparing effect can be expected when estrogen is administered concomitant with vitamin D3 rather than it is used alone". (4)

 

REFERENCES
4. I. Gorai et al. A comparative study on effect of Estrogen vs vitamin D on postmenopausal bone loss.
J Bone Miner. Res 1994; 9(Suppl 1): S 327

QUESTION
10. What are the differences and advantages of alfacalcidol versus plain vitamin D?
 
ANSWER

Plain vitamin D in high doses is effective in healing rickets and osteomalacia, i.e. diseases with severe vitamin D deficiency or resistance. In selected populations of elderly people with low vitamin D levels (vitamin D insufficiency) it will decrease PTH, slightly increase BMD, and thereby reduce the risk of fractures.

In the large number of osteoporotic patients who are replete in vitamin D, no significant effects can be expected from plain vitamin D. Nevertheless, very often calcium plus vitamin D supplements are given just to guarantee an optimal supply.

Also in patients under long-term corticoid therapy it has been shown that calcium plus plain vitamin D alone has no significant effect on BMD [1].

After intestinal absorption alfacalcidol will readily be activated in the liver into 1,25-dihydroxycholecalciferol (= calcitriol), i.e. the plasma level of this active hormone will be augmented inducing effects on calcium absorption, PTH, and bone turnover. This will never occur even with rather high doses of plain vitamin D because the second activation step in the kidney (1α-hydroxylase) is strongly regulated. Alfacalcidol, however, is already 1α-hydroxylated, and activation in the liver will take place quantitatively without registration.

Table 15 summarizes the most important differences between plain vitamin D and the active analogue alfacalcidol.

From a therapeutic point of view plain vitamin D can be used as a nutritional supplement in case of insufficient supply, while alfacalcidol is a specific antiosteoporotic drug.

Table 15      Plain vitamin D or active alfacalcidol ?

REFERENCES
1. Ringe JD, Faber H.
Calcium and vitamin D in the prevention and treatment of glucocorticoid-induced osteoporosis.
Clin Exp Rheymatol 2000; 18 Suppl 21: S44-S48

QUESTION
11. What is the rationale of using alfacalcidol in corticosteroid-in