Turner Syndrome And Bone Health

Overview

Turner syndrome (TS) is a rare genetic condition in biological females, where the second sex chromosome X is partially or completely missing.¹ This disease affects approximately 50 in 100,000 newborn girls.² Overall, women with TS have higher mortality rates compared to women without the condition.¹ The chromosomal defect caused by this condition is associated with a lack of certain genes that play a crucial role in various essential processes in our body. Patients with TS experience short stature (height), delayed puberty, ovarian failure, infertility, hypergonadotropic hypogonadism, type 1 and type 2 diabetes, heart complications, autoimmune disorders, and bone health issues, the latter which will be the main focus of this article.^3,4,5

Compromised bone health in patients with TS 

One of the complications of TS is a compromised bone health. Females with TS mineral deficiency in their bones, which results in bones being less dense and more fragile. Therefore, people with TS have a higher risk of experiencing  a bone fracture.⁶ Bones in the palm, forearm, lower back, and hip joint seem to be affected the most.⁷ Research has also reported that TS patients have a different bone geometry compared to the healthy individuals, which can change the robustness of the bones.⁸ Together, these factors increase the susceptibility for people with TS to develop osteoporosis.⁹ 

Causes of poor bone health in patients with TS 

Unfortunately, the exact cause of bone fragility in TS is yet to be found, but recent breakthroughs have been made. A potential cause of low bone mineral density is the loss of estrogen hormone production due to hypergonadotropic hypogonadism, which is observed in TS.⁹ 

However, some other contributing factors to the abnormal bone structure. Another hormone that can promote the fragile bone structure is the follicle-stimulating hormone (FSH), which is elevated in women with TS. Elevated levels of this hormone can decrease bone mass.⁷ 

Next, the vitamin D deficiency, which is another comorbidity of TS.⁹ The researchers found that some TS patients have different genes in the vitamin D receptor compared to people without this condition, which is essential for vitamin D functions in the body.¹⁰

Calcium deficiency in TS women also increases the fragility of bones.⁶ The subsequent autoimmune diseases that women can develop due to TS include celiac disease, inflammatory bowel disease, and hyperthyroidism, and can cause damage to the bones as well.⁹

Treatment for bone abnormalities in patients with TS

There are two main treatment options to improve bone health in TS patients: 

• Growth hormone treatment (GH)
• Estrogen replacement therapy (ERT)

These therapies are used in general for biological women with TS to overcome short stature, hormonal and ovary dysfunction, and other health conditions caused by TS.⁵ The results of GH to improve bone health are controversial due to limited research. Some positive effects of GH treatment include an increase in the mineral density of the bones and a positive impact on the bone geometry. Consequently reducing the fragility of bones and increasing their strength. However, some previous studies have reported either no effect or some negative effects of GH on bone mineral density.¹¹ 

Similarly, the results of ERT treatment have shown some uncertainty. The ERT has shown to be beneficial for increasing bone mineral density.^12,13 A different study demonstrated that the combination of hormones, in particular, estrogen and progestin, have a positive impact on bone mineral density.¹⁴ Lastly, some professionals recommend supplementing TS therapies with vitamin D and calcium, which are deficient and, therefore, can also aid in accomplishing healthy bone structure.^6,13

Side effects of GH and ERT treatments

The majority of treatments have some side effects, and GH and ERT are no exception. Although in general, the risk of developing the following side effects is considered very low under proper and suitable medical care.^13,15,16 

Side effects of GH include

• Increased blood sugar levels 
• Insulin resistance 
• Type 1 diabetes
• Slipped capital femoral epiphysis (SCFE)
• Induced tumour formation
• Benign Intracranial Hypertension (BIH) or Idiopathic Intracranial Hypertension (IIH)
• Pseudotumor cerebri
• Development of scoliosis or worsening of the existing scoliosis 
• Muscle and joint pain and swelling

Side effects of ERT include

• Breast tenderness or swelling 
• Vaginal bleeding or spotting 
• Mood swings and irritability
• Thromboembolic risk
• Breast cancer 
• Blood pressure changes 

Management of the bone health in TS

It is advised to check the bone mineral density and bone geometry of TS patients as soon as a diagnosis of TS is established. This helps identify people with an increased risk of poor bone health. These checks are achieved using peripheral quantitative computed tomography (pQCT), magnetic resonance imaging (MRI), or a non-invasive  non-radiation method such as phalangeal quantitative ultrasound (QUS).  ^7,17,18 These checks should be continued throughout the patient’s life and completed regularly during any GH or ERT treatments.⁷ Regular checks are also recommended to assess the calcium and vitamin D levels, ensuring an appropriate intake.⁶ Lastly, an overall healthy lifestyle and suitable physical activity is needed to maintain good overallhealth in people with TS.⁶

Diagnosis of TS and its complications 

The main challenge when improving bone health in women with TS is the initial diagnosis of the condition. TS is well-recognised within the medical industry and has a distinct presentation. The average age of diagnosis is 15 years, when impaired puberty becomes very noticeable.^3,19 Hence, the diagnosis of TS is often delayed until girls reach adolescence.^4,20 This in turn slows down the process of acquiring the appropriate treatment and medical care. 

The early diagnosis of TS and early initiation of ERT and GH treatment, has beneficial effects for TS overall and to decrease the risk of compromised bone health.^3,14 During the prenatal period, TS can be diagnosed using an ultrasound, and if certain abnormalities are observed it is followed by either the chorion villus sampling or amniocentesis tests, which are further used in karyotype analysis However, these are invasive methods.^3,5 

Non-invasive options, such as next-generation sequencing technologies, can be used onDNA so that the disease can be identified.²¹ However, this method is not always accurate and can produce errors, for example, if a baby’s samples are contaminated with DNA from the mother.^5,21 After birth karyotype analysis is the main diagnostic method for TS.²¹ Some other approaches were also found to be effective, such as chromosomal microarray.⁵ Researchers are working hard to develop new early detection methods for TS. For example, a recent study described the different abnormalities and defects that can be noted in oral and dental health of the females with TS, which can potentially be used to improve the early diagnosis.²⁰

Summary

TS is a rare genetic condition, which only affects biological females, where the second sex chromosome X is partially or completely missing. This leads to many complications, such as impaired bone health, which is caused by low bone mineral density and changes in bone geometry. The ultimate treatment for the fragility of bones is yet to be found. However, early diagnosis of TS along with the available treatment options, appropriate medical care, overall healthy lifestyle, and suitable physical activity have a positive impact on bone health in patients with TS. Once the diagnosis of TS is received, it is essential to complete the necessary tests to determine the status of the bone mineral density and bone geometry to ensure the healthy development of the bones and improvement of the existing bone health issues.