Hormone Therapy
Bisphosphonates
Evista (Raloxifene)
Protos (Strontium ranelate)
Potential Therapies

Hormone Therapy

Hormone therapy at the time of menopause may be beneficial for protecting bones.

The Women's Health Initiative Trial (published July 2002 and October 2003) has shown that hormone therapy as oestrogen plus progestin, does reduce the incidence of fractures at the hip and vertebrae (spinal bones) in postmenopausal women.^36,37 However, long-term use of this type of hormone therapy is associated with other risks of heart disease, breast cancer, pulmonary embolism (blood clots in the lung) and deep vein thrombosis (blood clots in the leg veins).³⁶ The Women's Health Initiative Trial of oestrogen alone in women who have had a hysterectomy has also shown a reduction in fracture risk along with no increase in heart disease or breast cancer, but a small increase in the risk of stroke in women aged 50 to 79 years.^92,93

Although hormone therapy has beneficial effects on bone health, it should be prescribed primarily for the short-term treatment (less than 5 years) of menopausal symptoms in women who are progressing through menopause.

The use of hormone therapy for disease prevention is not recommended. However, some women may elect to use hormone therapy. This needs to be done in consultation with the treating physician and with the woman understanding the risks and benefits of this therapy.³⁸

It is also important to realise that hormone therapy only protects your bones whilst on the treatment. Once hormone therapy is ceased, the rate of bone loss will return to the same level it was before starting hormone therapy.³⁹

Further Information on Hormone Therapy (Hormone Replacement Therapy)

Managing Menopause (The Jean Hailes Foundation for Women's Health) - Hormone Therapy

Bisphosphonates

Bisphosphonates are a class of drug, which function to decrease bone loss.

Fosamax and Actonel

Both Fosamax and Actonel have been found to reduce the incidence of vertebral (spinal bones) and hip fractures.^40,41 These drugs also reduce the risk of fracture at other sites in the body. The effects of these drugs on risk of fracture usually starts within 6 - 12 months of commencing therapy (some data on effects at 3 months).

These medications are generally well tolerated. They have been associated with side effects of heartburn, abdominal discomfort and ulceration of the oesophagus (food pipe). Ulceration of the oesophagus is one of the side effects that is most concerning. Hence, these medications must be taken first thing in the morning on an empty stomach, with a full glass of water and the individual needs to remain either sitting upright or standing for the next 30 minutes. After this time, normal activities and eating can be resumed. The incidence of oesophageal ulceration is extremely low when these medications are taken correctly.

These medications can be taken either daily or once weekly. There is an increasing trend for prescribing these medications once weekly as it improves compliance and it is likely to further reduce the incidence of gastrointestinal upset.³⁸ It is advisable that these medications are used cautiously in those with significant reflux oesophagitis (heartburn) and those with a hiatus hernia. These drugs are not well absorbed; hence it is important to take them on an empty stomach. It is also recommended not to take calcium at the same time as the bisphosphonate, as calcium may interfere with the absorption of the bisphosphonate.

Fosamax plus D, actonel combi and Actonel Combi D have all recently become available. Fosamax plus D® provides the added benefit of a weekly dose (2,800 IU) vitamin D; equivalent to 400 IU daily. (Refer to vitamin D [j1] section). Actonel combi® is also a combination medicine combining actonal and calcium with 7 tablets per pack: one actonel tablet once/week and 6 calcium carbonate 1250mg tablets for the other days of the week. Actonel Combi D® is a combination preparation containing once Actonal tablet taken once weekly and six sachets of  calcium carbonate and vitamin D which are mixed with water and taken daily for six days a week (excluding the day when the Actonal tablet is taken). (See calcium supplements)

Didrocal

Didrocal (Etidronate and Calcium) is administered in a somewhat different way to the other medications. This preparation is administered cyclically. For a two week period the active tablet Etidronate is taken twice daily. This is then followed by an 11 week period where a calcium tablet is taken once daily. This cycle is then repeated. This medication is generally well tolerated and does not have the problems with side effects of the upper gastrointestinal system such as heartburn or oesophageal ulceration. There may be side effects of diarrhoea or nausea. Generally this drug has been found to be effective in increasing bone mineral density and reducing the incidence of vertebral fractures (spinal column). This medication is probably best suited to women with osteoporosis of the spine.⁴²

Non oral forms of Bisphosphonates

If women are unable to tolerate the oral forms of the bisphosphonates, there is the option to have these forms of medication given intravenously in an intermittent fashion. In this setting it is necessary for women to be under the care of a specialised physician or osteoporosis clinic.

Considerations and Issues of Bisphosphonates

In order for bisphosphonates to be effective in increasing bone mineral density and reducing the likelihood of fracture, women need to ensure that they have an appropriate intake of calcium either through diet or supplements and that they also have adequate vitamin D levels. With Fosamax plus D, Actonal Combi and Actonel Combi D, these issues are in part addressed but would require further discussion with a woman's health professional. For women taking didrocal, there is no need to take additional calcium supplements, as these are already included in this preparation. There still may be a requirement for additional Vitamin D supplementation if the measured Vitamin D levels are low.

Bisphosphonates are primarily prescribed for women (and men) who have osteoporosis as defined on a bone DEXA scan and a history of an osteoporosis related (low trauma) fracture. In this setting the cost of these medications is subsidized by the Australian PBS.

There is also evidence to suggest that these medications may also prevent fractures in women with osteoporosis who do not have a history of fracture. There is evidence that the use of these medications in individuals on long-term corticosteroid therapy (eg prednisolone) also helps to prevent the development of osteoporosis. However, subsidized funding of these medications by the Australian PBS for these particular indications is not available. However, Actonel has been listed for use by the RPBS (for veterans) for the prevention of corticosteroid-induced osteoporosis. This drug can be used in individuals who have not had a fracture. However, there are certain criteria that the individual needs to satisfy in order to be prescribed Actonel for corticosteroid-induced osteoporosis.

Special Conditions - corticosteroid therapy

There are many unresolved issues with regards to the use of these medications. One issue is with regard to how long therapy with these drugs should be given. There are few studies using these medications beyond 7 years of therapy, although there is a published study with Fosamax, in which therapy was used for 10 years.⁹⁴ This study found that Fosamax was safe and resulted in a sustained increase in bone density. However, there was no data in regards to prevention of fracture from this study. Most physicians would therefore recommend using these medications until such a time that there is improvement in bone mineral density measurements and for only a few years (5-7 years). Hopefully as more studies become available and the duration of the studies is longer, then recommendations for longer-term use can be made.

Osteonecrosis of the jaw

Bisphosphonates have recently been linked to a rare potential side-effect: osteonecrosis of the jaw. Osteonecrosis of the jaw occurs when an area of exposed bone persists for more than 6 weeks after removal of a tooth. The risk appears to be very low with an estimated one in 2000-10 000 cases.⁹⁵  The majority of cases have occurred when patients have been taking potent, high dose intravenous bisphosphonates for management of bone malignancy. Although more uncommon, there have been some cases reported for those receiving oral bisphosphonates for the treatment of osteoporosis.⁹⁵

It is advisable to have a dental health check prior to commencing bisphosphonates. If a person is already taking bisphosphonates they should inform their dentist, particularly if they require a dental extraction.

It should be remembered that people with osteoporosis on bisphosphonates have a significantly reduced risk of fracture. This represents significant health benefits compared to the small risk of osteonecrosis of the jaw.⁹⁵  

Another issue is in regards to using bisphosphonates to prevent rather to treat established osteoporosis. This is not recommended, as studies to date have not shown a benefit in terms of preventing fractures in women who have osteopaenia (reduced bone mineral density as determined by a DEXA study, which is not as severe as that of osteoporosis).

Evista (Raloxifene)

This medication is known as a selective oestrogen-receptor modulator. It therefore acts at some sites in the body like oestrogen but at other sites of the body it functions as an anti-oestrogen. In bone it works as an oestrogen and leads to an increase in bone mass (density). In the breast and uterus it works as an anti-oestrogen and therefore does not stimulate the breast or uterine lining. Due to its anti-oestrogen effects in the breast, it reduces the incidence of breast cancer.

Primarily Evista (Raloxifene) has been shown to reduce the incidence of vertebral fractures (spinal column).⁴³ The evidence for this medication having a significant effect on fractures at other sites of the body is lacking.

The side effects of this therapy include hot flushes. This therapy is therefore problematic for premenopausal women and women who are currently going through menopause, as it may worsen menopausal symptoms. This therapy is best reserved for postmenopausal women who have gone through menopause. The other side effect of this therapy is a slightly increased risk of deep vein thrombosis. Hence, women who are on this medication need to consider stopping this therapy if they are going to be immobile for sometime, such as during long airline flights or during hospital admission. The medication can be resumed once mobility is regained. Any woman who has significant risk factors for a clotting disorder should not be prescribed this therapy.

In order for this therapy to be effective it is essential that women have adequate vitamin D levels and adequate dietary calcium intake. It may be necessary to have supplements of calcium and vitamin D if measured vitamin D levels are low or dietary calcium intake is inadequate.

Protos (Strontium ranelate)

This medication has recently become in Australia for postmenopausal osteoporosis but is not available for treatment of osteoporosis in men. It is taken in the form of granules mixed with water and should be taken at bedtime at least two hours after eating.

Strontium is a trace element that is naturally found within soft tissues, blood, teeth and bone. Its' mode of action is unclear, but it seems to lead to decreased bone loss and may enhance bone formation. Studies with this medication in postmenopausal women have shown a reduction in both vertebral (spinal), hip and other fractures.^48,49 It also appears to be well tolerated, but may be associated with side effects of diarrhoea. Like other osteoporosis therapies, there may be a requirement for additional vitamin D and calcium supplements if measured vitamin D levels are low or dietary calcium intake is insufficient.

Potential Therapies

Tibolone (Livial)

This therapy is a different form of hormone therapy for treating menopausal symptoms. Tibolone may not have the same stimulatory effects on the breast as standard forms of hormone therapy. However, this has yet to be evaluated in properly conducted clinical trials. There is evidence that it has beneficial effects on bone and leads to an increase in bone mineral density.⁴⁴ Studies are currently underway to evaluate the effects of this medication in terms of preventing osteoporosis in postmenopausal women and assessing whether it is effective in preventing fracture.

Parathyroid Hormone

This therapy became available in Australia in November 2003 and is as yet unlisted for use by the PBS. This hormone is administered daily via a subcutaneous (just below the skin) injection. It functions to increase bone formation⁴⁵ and also absorption of calcium from the gut and kidney. Calcium and vitamin D supplements may be necessary with this medication and if this is to be done it needs to be monitored under the care of a specialist physician. Most of the studies with this medication have only been for up to 2 years. In Australia, treatment will be limited to one 18-month course per lifetime. There appears to be a clear benefit in terms of reducing all types of fractures in postmenopausal women, except for hip fractures.^46,47 The lack of benefit in preventing hip fracture may have been due to the way the studies were designed. More research is needed in this area. Due to the expense and limited access of this therapy, it is not readily available to all Australians. Its prescription for use is confined to specialists in osteoporosis.

Content updated 27 July, 2009