Toss

Toss Uses, Dosage, Side Effects, Food Interaction and all others data.

Toss works by reducing bone breakdown and stimulating rebuilding of bone and therefore reduces the risk of fracture. The newly formed bone is of normal quality.

In general, it is believed that strontium ranelate is capable of affecting a rebalance in bone turnover in favour of bone formation by: (1) increasing osteoblast differentiation from progenitors, osteoblast activity and survival, as well as regulating osteoblast-induced osteoclastogenesis, and (2) decreasing osteoclast differentiation and activity, as well as increasing osteoclast apoptosis .

It has also been shown that strontium ranelate is capable of improving and strengthening various components of overall bone tissue quality like bone mineral density and bone microarchitecture .

Trade Name Toss
Generic Strontium Ranelate
Type Tooth Paste
Formula C12H6N2O8SSr2
Weight Average: 513.49
Monoisotopic: 513.795712
Protein binding

The binding of strontium to human plasma proteins is low (25%) and strontium has a high affinity for bone tissue .

Groups Approved, Withdrawn
Therapeutic Class Other preparations: Inhibiting bone resorption
Manufacturer Ind Swift Laboratories Ltd
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Toss
Toss

Uses

Toss is a non-hormonal medicine used to treat osteoporosis in postmenopausal women. Toss reduces the risk of fracture at the spine and at the hip

About osteoporosis: Your body is constantly breaking down old bone and making new bone tissue. If you have osteoporosis, your body breaks down more bone than it forms so that gradually bone loss occurs and your bones become thinner and fragile. This is especially common in women after the menopause (change of life). Many people with osteoporosis have no symptoms and you may not even know that you have it. However, osteoporosis makes you more likely to have fractures (break bones), especially in your spine, hips and wrists.

Toss is also used to associated treatment for these conditions: Severe Osteoporosis

How Toss works

The underlying pathogenesis of osteperosis involves an imbalance between bone resorption and bone formation. Osteoclasts are a kind of differentiated or specialized bone cell that breaks down bone tissue while osteoblasts are another set of differentiated bone cells that synthesize and rebuild bone tissue. When osteoclasts degrade bone tissue faster than the osteoblasts are capable of rebuilding the bone tissue, low or inadequate bone mass density and osteoperosis can resula One of the mechanisms with which strontium ranelate is thought to act is its functionality as an agonist of the extracellular calcium sensing receptors (CaSRs) of osteoblasts and osteoclasts . Ordinary interaction between calcium 2+ divalent cations with mature osteoclast CaSRs is known to induce osteoclast apoptosis. Subsequently, strontium 2+ divalent cations from strontium ranelate use can also bind CaSRs on osteoclasts to induce their apoptosis because of the strontium 2+ cation's close resemeblance to calcium 2+. Contact between extracelluar calcium 2+ and osteoclast CaSRs stimulates the phospholipase C (PLC) dependant breakdown of phosphatidylinositol 4,5-biphosphate (PIP2) into the two secondary messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Whereas the calcium-CaSRs interaction then performs IP3 Adependent translocation of nuclear factor NF-kB from the cytoplasm to the nucleus in mature osteoclasts, strontium-CaSRs interactions involves a DAG-PKC beta II (protein kinase C beta II) signalling pathway for translocating NF-kB from the cytoplasm to the nucleus in an IP3-independent manner. Although the calcium 2+ and strontium 2+ mediated signalling pathways are different, both CaSR interactions induce osteoclast apoptosis and are in fact capable of potentiating each other, leading to enhanced osteoclast apoptosis and decreased bone tissue degradation .

At the same time, given the simiarity between the calcium 2+ and strontium 2+ cations [A3152], strontium 2+ cations from strontium ranelate are seemingly also able to act as an agonist and stimulate the CaSRs on osteoblasts, possibly in tandem with various local osteoblast stimulatory growth factors like transforming growth factor β (TGF β) and/or bone morphogenetic proteins (BMPs), to stimulate cyclic D genes and early oncogenes like c-fos and egr-1 that can mediate the mitogenesis and proliferation of new or more osteoblasts . Moreover, although the involvement of the PLC mediated pathway may be a part of the signalling mechanism in osteoblasts following the stimulation of their CaSRs, this has not yet been fully elucidated .

Furthermore, strontium ranelate is also thought to be capable of stimulating osteoblasts to enhance the expression of osteoprotegerin while also concurrently reducing the expression of receptor activator of nuclear factor kappa-Β ligand (RANKL) in primary human osteoblastic cells. As osteoprotegerin can competitively bind to RANKL as a decoy receptor, which can prevent RANKL from binding to RANK, which is an activity that facilitates the signaling pathway for the differentiation and activaiton of osteoclasts. The subsequent net effect of these actions ultiamtely results in decreased osteoclastogenesis.

Moreover, bone biopsies obtained from patients treated with stronatium ranelate in clinical study reveal improvements in intrinsic bone tissue quality and microarchitecutre in ostepoerosis as evidenced by increased trabecular number, decreased trabecular separation, lower structure model index, and increased cortical thickness associated with a shift in trabecular structure from rod to plate like configurations compared with control patients .

Additionally, strontium from administered strontium ranelate is absorbed onto the crystal surface of treated bones and only slightly substitiutes for calcium in the apatite crystal of newly formed bone. As a result, there is an increased X-ray absorption of strontium as compared to calcium, which can lead to an amplification of bone mineral density (BMD) measurement by dual-proton X-ray absorptiometry. In essence, although strontium ranelate use can increase BMD some of the observations may be overestimations due to skeletal accretion of strontium in strontium ranelate treated patients .

Having the ability to both generate more osetoblasts and decrease the number of osteoclasts gives strontium ranelate an apparent dual mechanism of action when used to treat osteoperosis.

Dosage

Toss dosage

The recommended dose is one 2 gm sachet a day. Strontium should always be taken as per the advice of the doctor. Please check with your doctor in case of any confusion. Strontium is for oral use.

It is recommended that you take Strontium at bedtime. You may lie down immediately after taking Strontium if you wish. Take the granules contained in the sachets as a suspension in a glass of water (see instructions below). Strontium can interact with milk and milk products, so it is important that you mix Strontium only with water to be sure it works properly

Drink straight away. If for some reason you do not drink the medicine straight away, make sure you stir it again before drinking. You should not leave it more than 24 hours before you drink it. Your doctor may advise you to take calcium and vitamin D supplements in addition to Strontium. Do not take calcium supplements at bedtime, at the same time as Strontium. Your doctor will tell you how long you should continue to take Strontium. Osteoporosis therapy is usually required for a long period. It is important that you continue taking Strontium

If you forget to take Strontium: Do not take a double dose to make up for forgotten individual doses. Just carry on with the next dose at the normal time.

Side Effects

Like all medicines, Strontium can cause side effects, although not everybody gets them. The most common side effects are nausea, diarrhoea, headache and skin irritation. However,these effects were mild and short-lived and usually did not cause the patients to stop taking their treatment. Other events less commonly reported included blood clots, fainting fit, memory troubles and, in rare cases, seizures. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Toxicity

Strontium ranelate has been withdrawn worldwide owing to an increased adverse cardiac effects profile along with increased risk of venous thromboembolism (VTE) and various life threatening allergic reactions.

In pooled randomised placebo-controlled studies of post-menopausal osteoporotic patients, a significant increase in myocardial infarction has been observed in patients treated with strontium ranelate compared to placebo . Patients with significant risk factors for cardiovascular events (ie. hypertension, hyperlipidemia, diabetes mellitus, smoking) would be susceptible to an even higher risk of cardiac ishaemic events like myocardial infarction .

In phase III placebo-controlled studies, strontium ranelate treatment was associated with an increase in the annual incidence of venous thromboembolism (VTE), including pulmonary embolism. This places substantial risk on patients at risk of VTE and elderly (over 80 years) patients at risk of VTE who may be more commonly associated with illnesses or conditions leading to immobilisation .

Life-threatening cutaneous reactions like Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported with the use of strontium ranelate. In particular, a higher incidence of such reactions has been reported in patients of Asian origin.

In a pooled analysis of randomised placebo-controlled studies in post-menopausal osteoporotic patients, the most common adverse reactions consisted of nausea and diarrhea .

Nevertheless, good tolerance was shown in a clinical study investigating the repeated administration of 4 g strontium ranelate per day over 25 days in healthy postmenopausal women . Single administration of doses up to 11 g in healthy young male volunteers did not cause any particular symptoms .

In patients with mild to moderate renal impairment (30-70 ml/min creatine clearance), strontium clearance decreases as creatinine clearance decreases (approximately 30% decrease over the creatinine clearance range 30 to 70 ml/min) and thereby induces an increase in strontium plasma levels. However, no dosage adjustment is required for patients with miod to moderate renal impairment - although no pharmacokinetic data exists for patients with severe renal impairment associated with creatinine clearance below 30 ml/min .

There are no data from the use of strontium ranelate in pregnant women .

Physico-chemical data suggests strontium ranelate can be excreted into human milk. Strontium ranelate should not be used during breastfeeding .

No effects were observed on male and female fertility in animal studies .

Precaution

Before taking Toss talk to your doctor:

  • if you have severe kidney disease.
  • if you are being treated or have been treated for blood clots.
  • if you are confined to bed or if you are to undergo an operation. The risk of vein thrombosis (blood clots in the leg) may be increased in the event of lengthy immobilization.
  • if you are allergic (hypersensitive) to strontium ranelate.

Toss is not intended for use in children and adolescents. During treatment, if you experience an allergic reaction (such as swelling of the face, tongue or throat, difficulty in breathing or swallowing, skin rash), you must stop taking Toss and seek medical advice immediately. If you have stopped treatment due to hypersensitivity reactions you should not re-start therapy with Toss.

Interaction

Taking other medicines: Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. If you are taking medicines containing calcium, you should leave at least 2 hours before you take Toss . If you take antacids (medicines to relieve heartburn) you should take them at least 2 hours after Toss . If this is not possible, it is acceptable to take the two medicines at the same time. You should stop taking Toss if you have to take oral tetracyclines or quinolones (two types of antibiotics). You can take Toss again when you have finished taking these antibiotics. If you are unsure about this ask your doctor.

Taking Toss with food and drink: Food, milk and milk products reduce the absorption of strontium ranelate. It is recommended that you take Toss in-between meals, preferably at bedtime at least two hours after food, milk or milk products or calcium supplements.

Food Interaction

  • Avoid calcium supplements/calcium rich foods. Take strontium ranelate separated from calcium-containing food and supplements.
  • Take on an empty stomach. Take strontium ranelate between meals and at least 2 hours after eating at bedtime for optimal bioavailability.

Volume of Distribution

Strontium has a volume of distribution of about 1 L/kg .

Elimination Route

The absolute bioavailability of strontium is about 25% (within a range of 19-27%) after an oral dose of 2 g strontium ranelate. Maximum plasma concentrations are reached approximately 3-5 hours after a single dose of 2 g. Steady state is reached after 2 weeks of treatement. The intake of strontium ranelate with calcium or food reduces the bioavailablity of strontium ranelate by about 60-70%, compared with administration 3 hours after a meal .

Due to the relatively slow absorption of strontium, food and calcium intake should be avoided both before and after administration of strontium ranelate. Conversely, oral supplementation with vitamin D has no effect on strontium exposure whatsoever.

Half Life

The effective half-life of strontium is approximately 60 hours .

Clearance

The plasma dclearance is about 12 ml/min and its renal clearance is about 7 ml/min .

Elimination Route

The elimination of strontium is time and dose independent. Strontium excretion occurs via the kidneys and the gastrointetinal.

Pregnancy & Breastfeeding use

Pregnancy: Toss is meant for use only in postmenopausal women. Therefore, this should not be taken during pregnancy. If you take it by accident during pregnancy, stop taking it straight away and talk to your doctor.

Breast-feeding: Toss is meant for use only in postmenopausal women. Therefore, breast-feeding women should not take this medicine. If you take it by accident during breast- feeding, stop taking it straight away and talk to your doctor.

Contraindication

Toss is not intended for use in children and adolescents. During treatment, if you experience an allergic reaction (such as swelling of the face, tongue or throat, difficulty in breathing or swallowing, skin rash), you must stop taking Toss and seek medical advice immediately. If you have stopped treatment due to hypersensitivity reactions you should not re-start therapy with Toss

Acute Overdose

If you take too many sachets of Toss, tell your doctor. They may advise you to drink milk or take antacids to reduce the absorption of the active ingredient.

Storage Condition

Keep out of the reach and sight of children. Store at a cool and dry place, away from light

Innovators Monograph

You find simplified version here Toss

Toss contains Strontium Ranelate see full prescribing information from innovator Toss Monograph, Toss MSDS, Toss FDA label

FAQ

What is Toss used for?

Toss used to reduce bone pain, increase bone mineral density, and reduce the risk of some fractures. Toss may play a role in bone formation, and also may inhibit bone breakdown.

How safe is Toss?

Toss has never been approved in the U.S. Different from the ranelate compound and there have been no studies showing that they are safe or effective.

How does Toss work?

Toss work through dual mechanisms of inhibiting resorption by osteoclasts and maintaining or stimulating bone formation by osteoblasts.

What are the common side effects of Toss?

The common side effects of Toss are stomach pain, diarrhea, and headache in some people. Taking very high doses of Toss by mouth is possible. High doses of strontium might damage the bones.

Is Toss safe during pregnancy?

Toss ilikely safe during pregnancy and breast-feeding when taken by mouth in food amounts or when used in toothpaste.

Is Toss safe during breastfeeding?

Toss is likely safe during breast-feeding when taken by mouth in food amounts or when used in toothpaste.

How long Toss take to work?

Maximum plasma concentrations are reached approximately 3-5 hours after a single dose of 2 g. Steady state is reached after 2 weeks of treatement.

How long can I take Toss?

Taking another prescription form of Toss known as Toss ranelate by mouth for up to 10 years is possibley safe.

When should Toss be taken?

Toss should be taken at bed time, at least two hours after eating, so it can be absorbed properly. Wait at least two hours before having any food, although you can have water if you wish.

What does strontium do for the body?

Toss seems to play a role in how your body makes new bone while it slows the breakdown of old bone. That means it may affect how strong your bones are.

Is Toss good for osteopenia?

For several years now alternative doctors have recommended Toss citrate as a supplement in the treatment of osteopenia and as a preventive against osteoporosis.

Does Toss cause kidney stones?

The amount of Toss and apatite in kidney stones is correlated.

Is Toss highly radioactive?

Naturally occurring strontium is not radioactive.Toss is a silvery metal that rapidly turns yellowish in air.

How does Toss get into the body?

When you eat food or drink water containing Toss, only a small amount leaves the intestines and enters the blood.

Can I take Toss for a long time?

Long-term therapy with Toss has proven to be effective in reducing fracture risk, it is well tolerated and associated with a low incidence of side effects, making it a first-line treatment for postmenopausal women at high risk of fractures.

Is Toss harmful to humans?

Breathing or ingesting low levels of radioactive Toss have not been shown to affect health. High levels of radioactive Toss can damage bone marrow and cause anemia and prevent the blood from clotting properly.

Is Toss good for teeth?

Toss treatment may be beneficial in reducing loss of calcium from intact teeth-non-carious as well as carious-and this beneficial effect of Toss is unrelated to change in teeth hardness.

Is Toss safe for bones?

It seems to play a role in how your body makes new bone while it slows the breakdown of old bone. That means it may affect how strong your bones are. Some research says that women with osteoporosis may not absorb strontium as they should.

Can I take overdose of Toss?

Taking very high doses of Toss by mouth is pssibly unsafe. High doses of Toss might damage the bones.Toss might cause side effects such as stomach pain, diarrhea, and headache in some people. 

Can Toss be toxic?

There are no harmful effects of stable Toss  in humans at the levels typically found in the environment. The only chemical form of stable Toss that is very harmful by inhalation is Toss chromate, but this is because of toxic chromium and not Toss itself.

How much Toss can I take daily?

Toss likely safe when taken by mouth in amounts found in food. The typical diet includes 0.5-1.5 mg of Toss per day.

Is Toss flammable?

Not combustible but forms flammable gas on contact with water or damp air. . Use dry sand, special powder.

*** Taking medicines without doctor's advice can cause long-term problems.
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