Monitor for bone toxicity with prolonged retinoid use

WASHINGTON – In patients using continued or high doses of retinoids for indications other than acne, monitoring for bone side effects makes sense, Dr. John DiGiovanna said at the Atlantic Dermatological Conference.

The standard courses of isotretinoin used to treat acne have not been shown to be associated with decreased bone mineral density. In addition, recent data from a large, population-based Danish study of fractures including patients taking isotretinoin, acitretin, and topical retinoids showed that none of the retinoids was associated with a change in the risk of fracture at any skeletal site (Arch. Dermatol. 2010;146:478-82).

With prolonged use, however, patients with risk factors such as a family history of osteopenia or osteoporosis and those taking other medications that might contribute to decreased bone density need to be monitored, said Dr. DiGiovanna of the National Cancer Institute, Bethesda, Md.

There are no set rules for such monitoring. Lab tests every 3-6 months are a good starting point, Dr. DiGiovanna said. Also, consider obtaining a radiographic series every 3 years or more frequently if the patient is symptomatic. Imaging should include the cervical and thoracic spine, heels, knees, pelvis, shoulders, and any symptomatic areas.

Retinoid bone toxicity comes in three types: premature epiphyseal closure, diffuse idiopathic skeletal hyperostosis (DISH), and osteopenia/osteoporosis.

Data on the effects of isotretinoin on growth plates are limited, and have generally been associated with high doses, extended treatment duration, and underlying bone demineralization, Dr. DiGiovanna said.

Rare cases of premature closure of epiphyses have been reported in early studies in patients given high doses of retinoids, Dr. DiGiovanna said. He cited the case of a 6-year-old boy whose isotretinoin dose ranged from 0.5 to 4.5 mg/kg per day. At age 9, he reported periodic pain in his right knee, and a radiograph showed diffuse demineralization. At age 10, the pain recurred and imaging showed partial fusion of the proximal tibial growth plate (J. Amer. Acad. Derm. 1982;7:663-6).

In a second case, a 9-year-old boy with a history of high-dose isotretinoin (up to 5 mg/kg per day) for the rare disorder known as fibrodysplasia ossificans progressiva reported leg pain and showed evidence of arrested growth in the form of dense metaphyseal bands on imaging. Normal growth resumed after he discontinued isotretinoin (Am. J. Dis. Child. 1988;142:316-8).

For young children who need continued use of retinoids, a lower dose can be considered until the child achieves full height. Remind parents that the child may need to be re-treated once the epiphyses have fully closed.

DISH has been reported in patients taking retinoids for extended periods of 2 or more years, Dr. DiGiovanna said. In fact, DISH is common in the general population, and most of the time it is asymptomatic.

Some patients weather the bone effects, as in the case of a 52-year-old man with a history of frequent blistering due to generalized epidermolytic hyperkeratosis. Despite developing osteophytes related to stenosis of a neural foramen in the spine, the patient had no neurological symptoms, and wanted to continue retinoids for relief of his skin symptoms. He continues on his therapy and receives yearly MRIs and neurologic evaluations, Dr. DiGiovanna reported.

Regarding the association between retinoid therapy and bone demineralization or osteopenia, "the evidence is really very weak" and there are many risk factors to consider, said Dr. DiGiovanna. "But if you have a patient with a history of osteopenia, for example, a DEXA [dual-energy x-ray absorptiometry] scan is easy to obtain, and there is minimal exposure to radiation."

Remind potentially high-risk patients to stay active, maintain normal vitamin D levels with oral supplementation, and follow a healthy lifestyle, Dr. DiGiovanna said.

The bone density at Ward’s triangle also can be a confounding factor and lead to a misdiagnosis of osteoporosis, said Dr. DiGiovanna.

"Ward’s triangle is not an anatomic area; it is an area of lowest density in the femoral neck," and it is imprecise and positional, he emphasized. In fact, the consensus from osteoporosis experts is that osteoporosis should be measured using the total hip and spine, and not Ward’s triangle.

A randomized trial of acne patients on 1 mg/kg per day of isotretinoin vs. controls showed no significant difference in bone density after 6 months except at Ward’s triangle, he said (Arch. Dermatol. 1999;135:961-5).

Dr. DiGiovanna had no financial conflicts to disclose.

[email protected]

WASHINGTON – In patients using continued or high doses of retinoids for indications other than acne, monitoring for bone side effects makes sense, Dr. John DiGiovanna said at the Atlantic Dermatological Conference.

The standard courses of isotretinoin used to treat acne have not been shown to be associated with decreased bone mineral density. In addition, recent data from a large, population-based Danish study of fractures including patients taking isotretinoin, acitretin, and topical retinoids showed that none of the retinoids was associated with a change in the risk of fracture at any skeletal site (Arch. Dermatol. 2010;146:478-82).

With prolonged use, however, patients with risk factors such as a family history of osteopenia or osteoporosis and those taking other medications that might contribute to decreased bone density need to be monitored, said Dr. DiGiovanna of the National Cancer Institute, Bethesda, Md.

There are no set rules for such monitoring. Lab tests every 3-6 months are a good starting point, Dr. DiGiovanna said. Also, consider obtaining a radiographic series every 3 years or more frequently if the patient is symptomatic. Imaging should include the cervical and thoracic spine, heels, knees, pelvis, shoulders, and any symptomatic areas.

Retinoid bone toxicity comes in three types: premature epiphyseal closure, diffuse idiopathic skeletal hyperostosis (DISH), and osteopenia/osteoporosis.

Data on the effects of isotretinoin on growth plates are limited, and have generally been associated with high doses, extended treatment duration, and underlying bone demineralization, Dr. DiGiovanna said.

Rare cases of premature closure of epiphyses have been reported in early studies in patients given high doses of retinoids, Dr. DiGiovanna said. He cited the case of a 6-year-old boy whose isotretinoin dose ranged from 0.5 to 4.5 mg/kg per day. At age 9, he reported periodic pain in his right knee, and a radiograph showed diffuse demineralization. At age 10, the pain recurred and imaging showed partial fusion of the proximal tibial growth plate (J. Amer. Acad. Derm. 1982;7:663-6).

In a second case, a 9-year-old boy with a history of high-dose isotretinoin (up to 5 mg/kg per day) for the rare disorder known as fibrodysplasia ossificans progressiva reported leg pain and showed evidence of arrested growth in the form of dense metaphyseal bands on imaging. Normal growth resumed after he discontinued isotretinoin (Am. J. Dis. Child. 1988;142:316-8).

For young children who need continued use of retinoids, a lower dose can be considered until the child achieves full height. Remind parents that the child may need to be re-treated once the epiphyses have fully closed.

DISH has been reported in patients taking retinoids for extended periods of 2 or more years, Dr. DiGiovanna said. In fact, DISH is common in the general population, and most of the time it is asymptomatic.

Some patients weather the bone effects, as in the case of a 52-year-old man with a history of frequent blistering due to generalized epidermolytic hyperkeratosis. Despite developing osteophytes related to stenosis of a neural foramen in the spine, the patient had no neurological symptoms, and wanted to continue retinoids for relief of his skin symptoms. He continues on his therapy and receives yearly MRIs and neurologic evaluations, Dr. DiGiovanna reported.

Regarding the association between retinoid therapy and bone demineralization or osteopenia, "the evidence is really very weak" and there are many risk factors to consider, said Dr. DiGiovanna. "But if you have a patient with a history of osteopenia, for example, a DEXA [dual-energy x-ray absorptiometry] scan is easy to obtain, and there is minimal exposure to radiation."

Remind potentially high-risk patients to stay active, maintain normal vitamin D levels with oral supplementation, and follow a healthy lifestyle, Dr. DiGiovanna said.

The bone density at Ward’s triangle also can be a confounding factor and lead to a misdiagnosis of osteoporosis, said Dr. DiGiovanna.

"Ward’s triangle is not an anatomic area; it is an area of lowest density in the femoral neck," and it is imprecise and positional, he emphasized. In fact, the consensus from osteoporosis experts is that osteoporosis should be measured using the total hip and spine, and not Ward’s triangle.

A randomized trial of acne patients on 1 mg/kg per day of isotretinoin vs. controls showed no significant difference in bone density after 6 months except at Ward’s triangle, he said (Arch. Dermatol. 1999;135:961-5).

Dr. DiGiovanna had no financial conflicts to disclose.

[email protected]

WASHINGTON – In patients using continued or high doses of retinoids for indications other than acne, monitoring for bone side effects makes sense, Dr. John DiGiovanna said at the Atlantic Dermatological Conference.

The standard courses of isotretinoin used to treat acne have not been shown to be associated with decreased bone mineral density. In addition, recent data from a large, population-based Danish study of fractures including patients taking isotretinoin, acitretin, and topical retinoids showed that none of the retinoids was associated with a change in the risk of fracture at any skeletal site (Arch. Dermatol. 2010;146:478-82).

With prolonged use, however, patients with risk factors such as a family history of osteopenia or osteoporosis and those taking other medications that might contribute to decreased bone density need to be monitored, said Dr. DiGiovanna of the National Cancer Institute, Bethesda, Md.

There are no set rules for such monitoring. Lab tests every 3-6 months are a good starting point, Dr. DiGiovanna said. Also, consider obtaining a radiographic series every 3 years or more frequently if the patient is symptomatic. Imaging should include the cervical and thoracic spine, heels, knees, pelvis, shoulders, and any symptomatic areas.

Retinoid bone toxicity comes in three types: premature epiphyseal closure, diffuse idiopathic skeletal hyperostosis (DISH), and osteopenia/osteoporosis.

Data on the effects of isotretinoin on growth plates are limited, and have generally been associated with high doses, extended treatment duration, and underlying bone demineralization, Dr. DiGiovanna said.

Rare cases of premature closure of epiphyses have been reported in early studies in patients given high doses of retinoids, Dr. DiGiovanna said. He cited the case of a 6-year-old boy whose isotretinoin dose ranged from 0.5 to 4.5 mg/kg per day. At age 9, he reported periodic pain in his right knee, and a radiograph showed diffuse demineralization. At age 10, the pain recurred and imaging showed partial fusion of the proximal tibial growth plate (J. Amer. Acad. Derm. 1982;7:663-6).

In a second case, a 9-year-old boy with a history of high-dose isotretinoin (up to 5 mg/kg per day) for the rare disorder known as fibrodysplasia ossificans progressiva reported leg pain and showed evidence of arrested growth in the form of dense metaphyseal bands on imaging. Normal growth resumed after he discontinued isotretinoin (Am. J. Dis. Child. 1988;142:316-8).

For young children who need continued use of retinoids, a lower dose can be considered until the child achieves full height. Remind parents that the child may need to be re-treated once the epiphyses have fully closed.

DISH has been reported in patients taking retinoids for extended periods of 2 or more years, Dr. DiGiovanna said. In fact, DISH is common in the general population, and most of the time it is asymptomatic.

Some patients weather the bone effects, as in the case of a 52-year-old man with a history of frequent blistering due to generalized epidermolytic hyperkeratosis. Despite developing osteophytes related to stenosis of a neural foramen in the spine, the patient had no neurological symptoms, and wanted to continue retinoids for relief of his skin symptoms. He continues on his therapy and receives yearly MRIs and neurologic evaluations, Dr. DiGiovanna reported.

Regarding the association between retinoid therapy and bone demineralization or osteopenia, "the evidence is really very weak" and there are many risk factors to consider, said Dr. DiGiovanna. "But if you have a patient with a history of osteopenia, for example, a DEXA [dual-energy x-ray absorptiometry] scan is easy to obtain, and there is minimal exposure to radiation."

Remind potentially high-risk patients to stay active, maintain normal vitamin D levels with oral supplementation, and follow a healthy lifestyle, Dr. DiGiovanna said.

The bone density at Ward’s triangle also can be a confounding factor and lead to a misdiagnosis of osteoporosis, said Dr. DiGiovanna.

"Ward’s triangle is not an anatomic area; it is an area of lowest density in the femoral neck," and it is imprecise and positional, he emphasized. In fact, the consensus from osteoporosis experts is that osteoporosis should be measured using the total hip and spine, and not Ward’s triangle.

A randomized trial of acne patients on 1 mg/kg per day of isotretinoin vs. controls showed no significant difference in bone density after 6 months except at Ward’s triangle, he said (Arch. Dermatol. 1999;135:961-5).

Dr. DiGiovanna had no financial conflicts to disclose.

[email protected]