Calvarial Doughnut Lesions–Bone Fragility Syndrome

Calvarial doughnut lesions–bone fragility syndrome is a rare, inherited bone disease. Bones break easily from childhood. The skull shows small round “doughnut-like” hard areas on X-rays. Many people have low bone mineral density. Some have short height, curved long bones, or spine changes. The main gene is SGMS2, which affects a lipid (sphingomyelin) important for normal bone mineralization. Doctors diagnose it by signs, bone scans, and genetic testing. There is no single cure. Care focuses on stronger bones, fewer fractures, safe movement, and surgery when needed. NCBI+2NCBI+2

Calvarial doughnut lesions–bone fragility syndrome (often shortened to CDL) is a rare, inherited bone disorder. People with CDL have weaker bones that break more easily and have special ring-shaped (“doughnut-like”) spots in the skull bones that doctors can see on imaging. The condition usually starts in childhood. It is passed down in families in an autosomal dominant way (a change in just one copy of the gene is enough). The gene involved is SGMS2, which makes an enzyme (sphingomyelin synthase 2) important for building healthy bone. Harmful changes (variants) in this gene disturb bone mineralization and lead to low bone mineral density, fractures, and the doughnut-shaped skull lesions. PubMed+3NCBI+3NCBI+3

CDL is a genetic bone disease where bones are less dense and break easily, and the skull shows multiple ring-like sclerotic areas. The problem comes from a pathogenic variant in the SGMS2 gene. This gene helps make sphingomyelin, a key fat within cell membranes. When SGMS2 does not work properly, bone does not mineralize normally. As a result, children (and sometimes babies) have spinal and limb fractures, and later can develop visible, firm bumps on the skull that match the “doughnut” lesions seen on X-rays or CT scans. Some families have mild disease; others have severe disease with short stature and spine changes. MDPI

Another names

• Familial doughnut lesions of the skull

• Calvarial doughnut lesions with bone fragility

• CDL (Calvarial Doughnut Lesions)
  These names all refer to the same autosomal dominant condition linked to SGMS2. NCBI

Types

Doctors think of CDL as a spectrum caused by SGMS2 variants:

1. Classic CDL (childhood-onset osteoporosis + calvarial doughnut lesions). Low bone mineral density, recurrent fractures, and ring-shaped skull lesions that often appear later in childhood. MDPI

2. CDL with spondylometaphyseal dysplasia (severe form). Very early (even neonatal) fractures, short stature, spinal changes (platyspondyly), and thickened skull; still due to SGMS2 but often with specific missense variants. MDPI+1

3. SGMS2-related primary osteoporosis without obvious skull lesions (milder end). Some individuals with SGMS2 variants mainly have low bone density and fractures; skull findings may be subtle or appear later. PMC

Causes

Important note: The primary cause of CDL is a pathogenic variant in the SGMS2 gene. The items below explain the gene cause and common modifiers/triggers that can worsen bone fragility in someone who already has SGMS2-related disease. Environmental factors alone do not cause CDL without the SGMS2 variant.

1. SGMS2 nonsense variant (e.g., c.148C>T; p.Arg50Ter). Produces a nonfunctional enzyme and is the most repeatedly reported change worldwide. MDPI+1

2. SGMS2 missense variants (e.g., p.Ile62Ser, p.Met64Arg). Lead to mis-trafficking of the enzyme and a more severe form with skeletal dysplasia. MDPI+1

3. Autosomal-dominant inheritance. One affected parent can pass the variant to each child with a 50% chance. NCBI

4. Haploinsufficiency or loss of function in SGMS2. Reduced sphingomyelin synthesis impairs bone mineralization. PMC

5. Disordered osteoblast–osteoclast signaling secondary to SGMS2 defect. Altered membrane lipids can change pathways that control bone formation and resorption. PMC

6. Lower bone mineral density from defective matrix mineralization. A core biological effect of SGMS2 variants. NCBI

7. Age-related appearance of skull lesions. The diploic space of the skull develops with age, so lesions often appear or enlarge later in childhood. MDPI

8. Family-specific variant hotspots (e.g., recurrent p.Arg50Ter). Explains clustering in certain families/populations. MDPI

9. Low vitamin D status (modifier). Worsens osteoporosis in any condition, including CDL. (General bone health principle; used to optimize care.) MDPI

10. Low dietary calcium (modifier). Can further reduce bone mineralization. (Supportive management target.) MDPI

11. Glucocorticoid exposure (modifier). Steroids can reduce bone formation and should be minimized if possible. (General osteoporosis principle.) MDPI

12. Prolonged immobilization (modifier). Reduces bone strength through disuse. (General principle relevant to fracture care.) MDPI

13. Recurrent childhood fractures (consequence that perpetuates fragility). Fractures lead to deconditioning and more risk. NCBI

14. High bone turnover (e.g., ALP elevations). Reflects active bone remodeling in some patients. MalaCards

15. Mechanical stress at the skull vault (local contributor). May help explain the growth of ring-like lesions in affected calvarial bone. MDPI

16. Coexisting scoliosis or vertebral wedging (structural stressor). Increases future fracture risk. MDPI

17. Dental enamel defects (supporting sign). Indicate mineralization problems that also affect bone. MalaCards

18. Possible ocular issues (e.g., glaucoma in some families) (associated feature). May relate to connective/bone tissue changes around the orbit. MDPI

19. Facial nerve palsy in some families (associated feature). Highlights broader cranial involvement in this syndrome. MDPI

20. Genetic background and penetrance differences. Not everyone with the same variant is equally affected; severity varies within and across families. MDPI

Symptoms and signs

1. Easy bone fractures. People often break bones from mild injuries, especially in the spine and long bones, starting in childhood. NCBI

2. Low bone mineral density (osteoporosis/osteopenia). A bone scan (DXA) shows reduced density compared with age-matched values. NCBI

3. Skull “doughnut” lesions. Imaging shows ring-shaped areas in the skull bones; the scalp may feel firm bumps where the outer skull is thickened. MDPI+1

4. Back pain. Often due to vertebral compression fractures and wedging. MDPI

5. Short stature (in severe cases). Growth can be affected when fractures start very early. NCBI

6. Spine curve (scoliosis). The spine may curve sideways over time. NCBI

7. Flattened vertebral bodies (platyspondyly). Seen on spine X-rays. NCBI

8. Limb deformity (bowing). Repeated fractures can lead to bone shape changes. NCBI

9. Headaches or head tenderness. Sometimes due to palpable skull lesions. MDPI

10. Dental caries and enamel hypoplasia. Teeth may have weak enamel and frequent cavities. MalaCards

11. Elevated alkaline phosphatase on blood tests. A lab clue of active bone turnover in some patients. MalaCards

12. Facial nerve palsy (in some families). Episodes of weakness in facial muscles can happen and then improve. MDPI

13. Hearing issues (occasionally). Mixed hearing loss has been listed among features in databases. NCBI

14. Eye problems (rare). Some patients/families report glaucoma. MDPI

15. Normal intelligence and development in most. Motor delays can occur mainly when fractures and pain limit activity. NCBI

Diagnostic tests

A. Physical examination 

1. General musculoskeletal exam. Look for tenderness over long bones and spine, limited movement after fractures, and limb deformities. MDPI

2. Height/weight and growth charting. Track stature; short stature suggests the severe end of the spectrum. NCBI

3. Spinal inspection for scoliosis and kyphosis. Visual check and forward-bend test for curves that often accompany vertebral fractures. NCBI

4. Skull palpation. Feel for firm, round bumps over the frontal, parietal, or occipital bones that match calvarial lesions on imaging. MDPI

5. Neurologic and cranial nerve exam. Screen for facial nerve weakness and balance/hearing issues. MDPI

B. Manual/bedside procedures

1. Gait and functional assessment. Check walking, balance, and fall risk after fractures. NCBI
2. Spine percussion and range-of-motion. Gentle tap and movement checks may reveal painful vertebrae from compression fractures. MDPI
3. Beighton or joint laxity check (contextual). Not part of CDL itself but helps exclude other hypermobility disorders if suspected. (Differential diagnostic context.) MDPI
4. Dental inspection. Look for enamel defects and caries that support a systemic mineralization problem. MalaCards
5. Vision screening and intraocular pressure referral. If there is family history of glaucoma, early ophthalmology input is helpful. MDPI

C. Laboratory and pathological tests 

1. Serum alkaline phosphatase (ALP). Can be elevated; helps flag high bone turnover in some patients. MalaCards
2. Serum calcium, phosphate, and parathyroid hormone. Usually checked to rule out other metabolic bone diseases and optimize management. MDPI
3. 25-hydroxy vitamin D. Identify deficiency because it worsens osteoporosis; correct as part of care. MDPI
   14) Bone turnover markers (e.g., PINP, CTX). Supportive information on bone formation/resorption status. MDPI
4. Genetic testing for SGMS2. Targeted analysis for the recurrent c.148C>T (p.Arg50Ter) variant or sequencing of the SGMS2 coding region; confirms diagnosis. NCBI
5. Bone biopsy (selected cases). Prior studies show low and uneven mineralization with disorganized collagen—helps in complex cases or research settings. MDPI

D. Electrodiagnostic tests 

1. Facial nerve conduction studies/EMG (if recurrent palsy). Characterize nerve involvement when symptoms are present. MDPI
2. Audiology with tympanometry and pure-tone testing. Check for any mixed hearing loss reported in some individuals. NCBI

E. Imaging tests 

1. Plain skull X-rays. Show multiple ring-like sclerotic lesions (“doughnut lesions”) in the calvaria. Radiopaedia
2. Head CT or MRI. Detect small diploic lesions earlier; CT defines the sclerotic rim; MRI helps rule out other skull masses. MDPI
3. Skeletal survey (X-rays of long bones, pelvis, spine). Looks for fractures, bowing, and vertebral wedging/platyspondyly. MDPI
4. Dual-energy X-ray absorptiometry (DXA). Measures bone mineral density to stage osteoporosis and monitor treatment. NCBI
5. Spine lateral radiographs. Identify compression fractures and biconcave vertebrae. MDPI
6. Bone scintigraphy (sometimes). In CDL, scans can be surprisingly “quiet” compared with osteogenesis imperfecta, helping with the differential. MDPI
7. High-resolution peripheral CT (if available). Research/advanced imaging to study bone micro-architecture; not required for diagnosis. PMC

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Non-pharmacological treatments (therapies and other supports)

1. Fracture-safe physical therapy
   Description: A therapist teaches safe ways to move, roll, sit, stand, transfer, and walk. Training builds muscle strength and balance without impact. Sessions start slow and increase as tolerated. Home exercises are simple: gentle range-of-motion, core strength, and posture work. Purpose: reduce falls, protect bones, keep joints flexible, and improve daily function. Mechanism: stronger muscles unload brittle bones; better balance prevents falls; careful handling avoids micro-trauma. PMC+1

2. Hydrotherapy (water exercise)
   Description: Warm-water walking, gentle kicking, and floating exercises. Buoyancy supports the body so joints feel lighter. Purpose: move safely with less pain and less fracture risk. Mechanism: water reduces joint load and impact while resistance builds endurance and strength. OI Foundation

3. Progressive resistance training under supervision
   Description: Light bands or body-weight moves, increased slowly. Avoid jerks and high impact. Purpose: raise muscle strength and bone stimulus safely. Mechanism: muscle pull on bone signals bone-building cells, improving bone quality over time. Dove Medical Press

4. Weight-bearing practice with bracing
   Description: Standing frames, ankle-foot orthoses, or knee-ankle-foot braces support alignment during safe standing/walking. Purpose: allow bone to “feel” controlled load. Mechanism: weight bearing triggers bone remodeling and slows bone loss. Physiopedia

5. Fall-prevention program
   Description: Home safety scan (remove cords, use non-slip mats, good lighting), balance training, and hip protectors when appropriate. Purpose: cut fracture risk. Mechanism: fewer falls → fewer breaks; padded areas absorb energy in a fall. Medscape

6. Activity modification & safe handling
   Description: Teach families safe lifting, dressing, bathing, and transfers. Avoid twisting, sudden pulls, and contact sports. Purpose: prevent avoidable injuries. Mechanism: gentle, aligned movement lowers mechanical stress on fragile bones. PMC

7. Occupational therapy (OT)
   Description: OT adapts daily tasks, school/work setups, and recommends tools (grabbers, raised seats, ergonomic desks). Purpose: independence and joint protection. Mechanism: better body mechanics reduce micro-trauma and fatigue. Dove Medical Press

8. Orthotics and custom footwear
   Description: Shoe inserts, heel lifts, and supportive boots correct malalignment and reduce pain. Purpose: improve gait stability. Mechanism: alignment spreads load more evenly, lowering focal stress. Dove Medical Press

9. Spinal posture care
   Description: Posture training, core strengthening, and seating supports help scoliosis or kyphosis symptoms. Purpose: reduce pain and protect the ribcage and lungs. Mechanism: neutral spine lowers strain on vertebrae and ribs. Medscape

10. Vitamin D & calcium optimization (lifestyle)
    Description: Ensure daily intake from food and safe sun; supplement only if low, under clinician guidance. Purpose: support mineralization. Mechanism: vitamin D boosts calcium absorption; calcium supplies the mineral for bone. Office of Dietary Supplements+1

11. Protein-adequate diet
    Description: Include lean proteins (eggs, fish, legumes). Purpose: provide building blocks for bone matrix (collagen). Mechanism: amino acids form collagen; collagen is the scaffold for mineral deposition. PubMed

12. Pain self-management skills
    Description: Heat/cold packs, relaxation breathing, pacing, and sleep hygiene. Purpose: reduce pain flare-ups and improve energy. Mechanism: pain control lowers stress hormones that can worsen fatigue and activity limits. Medscape

13. Bone-safe school/work plans
    Description: Seating near exits, extra time for class changes, elevator use, and light backpacks. Purpose: reduce accidental trauma. Mechanism: less carrying and crowd impact lowers fracture risk. Dove Medical Press

14. Fracture care pathways
    Description: Early imaging, gentle immobilization, and protected mobilization after breaks. Purpose: faster healing with fewer complications. Mechanism: stable alignment supports callus formation and recovery. Medscape

15. Bone health education for caregivers
    Description: Teach red flags, safe play, and medicine timing. Purpose: empower families. Mechanism: informed choices prevent avoidable injuries and improve adherence. PMC

16. Sunlight & outdoor time (within safety)
    Description: Short, safe sun exposure as advised. Purpose: natural vitamin D synthesis. Mechanism: UVB triggers skin production of vitamin D3, supporting calcium absorption. Office of Dietary Supplements

17. Smoking and alcohol avoidance
    Description: Do not smoke; limit alcohol. Purpose: protect bone formation. Mechanism: both harm osteoblast function and raise fall risk. Medscape

18. Weight management
    Description: Keep a healthy weight with diet and gentle activity. Purpose: reduce joint load and falls. Mechanism: better strength-to-weight ratio improves balance and gait. Medscape

19. Assistive mobility devices
    Description: Canes, walkers, wheelchairs when needed. Purpose: safe mobility while healing. Mechanism: devices unload painful bones and control balance losses. Dove Medical Press

20. Multidisciplinary clinic care
    Description: Genetics, endocrinology, orthopedics, PT/OT, dentistry, and eye care as needed. Purpose: whole-person support. Mechanism: coordinated decisions lower complications and improve quality of life. Frontiers

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Drug treatments

Always prescribe by a specialist. Doses are typical adult label doses unless noted. Some agents are not approved for children or for OI/CDL-BFS but are used by extrapolation. Check renal function, calcium/vitamin D, dental status (osteonecrosis risk), and pregnancy warnings.

1. Zoledronic acid (Reclast®) – class: IV bisphosphonate. Dose/time: 5 mg IV once yearly (osteoporosis label). Purpose: reduce fractures and raise BMD. Mechanism: blocks osteoclast bone resorption, allowing bone to mineralize. Side effects: acute-phase reactions, hypocalcemia, rare ONJ/atypical femur fracture. Note: widely used in brittle bone disorders under specialist care. FDA Access Data

2. Alendronate (Fosamax®) – class: oral bisphosphonate. Dose/time: 70 mg once weekly (or 10 mg daily). Purpose: fracture risk reduction. Mechanism: osteoclast inhibition. Side effects: esophagitis if not taken upright/with water; rare ONJ/atypical femur fracture. FDA Access Data+1

3. Risedronate (Actonel®) – class: oral bisphosphonate. Dose/time: 35 mg once weekly (other regimens exist). Purpose: reduce vertebral and non-vertebral fractures. Mechanism: inhibits osteoclasts. Side effects: GI upset; rare ONJ/atypical femur fracture. FDA Access Data

4. Ibandronate (Boniva®) – class: oral or IV bisphosphonate. Dose/time: 150 mg monthly (oral) or 3 mg IV every 3 months. Purpose: vertebral fracture risk reduction. Mechanism: osteoclast inhibition. Side effects: dyspepsia (oral), acute-phase symptoms (IV). FDA Access Data+1

5. Pamidronate (Aredia®) – class: IV bisphosphonate. Dose/time: cycles vary; used off-label in pediatric brittle bone protocols. Purpose: improve BMD and reduce fractures in moderate-severe fragility syndromes. Mechanism: osteoclast inhibition. Side effects: fever, hypocalcemia, renal effects. (FDA label is for other indications; use in OI/CDL-BFS is off-label with published benefit in OI.) FDA Access Data+1

6. Denosumab (Prolia®) – class: RANKL inhibitor (monoclonal antibody). Dose/time: 60 mg subcutaneously every 6 months. Purpose: strong antiresorptive for high-risk adults. Mechanism: blocks osteoclast formation and function. Side effects: hypocalcemia (esp. CKD), infections, rare ONJ/atypical femur fracture; rebound risk if stopped without plan. FDA Access Data

7. Teriparatide (Forteo®; PTH 1-34) – class: anabolic. Dose/time: 20 mcg SC daily; limited duration per label. Purpose: build new bone in very high-risk adults (not for children). Mechanism: intermittent PTH stimulates osteoblasts. Side effects: hypercalcemia, dizziness; black-box warnings updated—use per label. FDA Access Data

8. Abaloparatide (Tymlos®) – class: PTHrP analog, anabolic. Dose/time: 80 mcg SC daily; limited duration. Purpose: rapid BMD gains in very high-risk adults. Mechanism: stimulates bone formation with transient resorption. Side effects: orthostatic symptoms, hypercalciuria. FDA Access Data

9. Romosozumab (Evenity®) – class: sclerostin inhibitor (dual effect: ↑formation, ↓resorption). Dose/time: 210 mg SC monthly for 12 months. Purpose: large spine and hip BMD increases in very high-risk adults. Mechanism: frees Wnt signaling in osteoblasts. Safety note: boxed warning for potential increased risk of MI/stroke—avoid in patients with recent cardiovascular events. FDA Access Data

10. Calcitonin-salmon (Miacalcin®) – class: antiresorptive peptide. Dose/time: 200 IU nasal daily (selected situations). Purpose: modest pain relief after vertebral fracture; limited BMD benefit. Mechanism: directly inhibits osteoclasts. Side effects: rhinitis; signal for malignancy risk—use only when benefits outweigh risks. FDA Access Data

11. Raloxifene (Evista®) – class: SERM. Dose/time: 60 mg daily in postmenopausal women. Purpose: vertebral fracture risk reduction when other agents are not suitable. Mechanism: estrogen agonist on bone, antagonist on breast/uterus. Side effects: VTE risk, hot flashes. FDA Access Data

12. Estradiol (Climara® transdermal) – class: systemic estrogen (with progestin if uterus present). Dose/time: per label. Purpose: prevention of postmenopausal osteoporosis in appropriate patients with menopausal symptoms; not first-line for fracture treatment. Mechanism: reduces bone resorption. Side effects: VTE, stroke, breast tenderness; use lowest dose for shortest time. FDA Access Data

13. Conjugated estrogens/bazedoxifene (Duavee®) – class: tissue-selective estrogen complex. Use: prevention of postmenopausal osteoporosis with vasomotor symptoms when appropriate. Mechanism/risks: estrogen effects with SERM protection on endometrium; observe VTE risks. (FDA label available; include only when clinically appropriate.) FDA Access Data

14. Calcium supplements – class: mineral supplement. Dose: usually 1000–1200 mg elemental calcium/day from diet + pills combined; adjust to age/sex. Purpose: ensure substrate for mineralization (but not a stand-alone fracture therapy). Mechanism: supplies calcium for bone. Side effects: constipation; kidney stone risk in high doses. Office of Dietary Supplements

15. Vitamin D3 (cholecalciferol) – class: vitamin. Dose: individualized to reach adequate 25-OH-D (often 800–2000 IU/day in adults unless deficient). Purpose: correct deficiency to support any bone drug. Mechanism: increases calcium absorption. Side effects: hypercalcemia in overdose. Office of Dietary Supplements

16. Calcitriol (active vitamin D) – Rx only
    Use: selected patients with impaired activation (e.g., renal disease) and symptomatic hypocalcemia under specialist care. Mechanism: active hormone form drives calcium absorption. Risks: hypercalcemia/hyperphosphatemia; monitor closely. (FDA-labeled; clinician-directed.) Office of Dietary Supplements

17. Analgesics (acetaminophen) – class: non-opioid pain reliever. Use: short-term fracture pain to keep patients mobile. Mechanism: central COX effects reduce pain. Risks: hepatotoxicity in overdose; stay within label. (General label evidence; adjunct only.)

18. Short-course NSAIDs (e.g., ibuprofen/naproxen) – class: anti-inflammatory. Use: acute fracture or post-op pain when not contraindicated. Mechanism: COX inhibition reduces inflammation and pain. Risks: GI/renal; caution post-fusion due to bone healing concerns—surgeon guidance needed. (Adjunct only.)

19. Opioids for severe acute fracture pain (e.g., tramadol) – brief use only
    Purpose: enable safe transfers and sleep during acute pain. Mechanism: μ-receptor analgesia. Risks: sedation, dependence; taper quickly; avoid chronic use. (Label-directed, last resort.)

20. rhBMP-2 (INFUSE® Bone Graft) – surgical adjunct
    Class: osteoinductive biologic placed locally by surgeons for specific indications (e.g., spine, tibia, oral/maxillofacial). Purpose: stimulate local bone formation in select procedures (not a systemic drug). Mechanism: BMP-2 signals progenitor cells to form bone. Risks: swelling, ectopic bone, specific contraindications; use only in approved indications. FDA Access Data+1

Important notes: Many medicines above are not specifically approved for CDL-BFS; they are used by analogy to osteoporosis/osteogenesis imperfecta (OI). Pediatric use, pregnancy, renal function, dental health, and cardiovascular risk must be reviewed by specialists before treatment. Evidence in OI shows bisphosphonates can cut pain and fractures and improve mobility; clinicians often adapt those protocols for severe genetic bone fragility. PubMed+1

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Dietary molecular supplements

1. Vitamin D3 – Dose: individualized to keep 25-OH-D sufficient (often 800–2000 IU/day in adults unless otherwise directed). Function: helps the gut absorb calcium and phosphate. Mechanism: turns on calcium transporters and bone mineralization genes. Tip: take regularly; monitor levels. Office of Dietary Supplements

2. Calcium (diet first, supplement to fill the gap) – Dose: usually 1000–1200 mg/day total intake. Function: main bone mineral. Mechanism: supplies calcium for hydroxyapatite crystals in bone. Tip: split doses ≤600 mg at a time for better absorption. Office of Dietary Supplements

3. Vitamin K (K1 and K2) – Dose: from food or a standard multivitamin; high-dose K2 is research-grade only. Function: activates osteocalcin, which binds calcium to bone. Mechanism: carboxylation of bone proteins. Note: talk to your doctor if you take blood thinners. PMC+1

4. Magnesium – Dose: RDA level by age/sex, usually 300–420 mg/day from diet/supplement. Function: cofactor for bone matrix and vitamin D metabolism. Mechanism: supports osteoblast function and mineral transport. Office of Dietary Supplements

5. Collagen peptides – Dose: common trial doses ~5–10 g/day. Function: provides amino acids for bone collagen. Mechanism: may improve bone turnover markers and BMD in postmenopausal women; use as adjunct, not a drug. PubMed

6. Protein (dietary) – Dose: 1.0–1.2 g/kg/day total protein for many adults (individualize). Function: supports muscle and bone matrix. Mechanism: amino acids build collagen and muscle, which protects bone. Bone Health & Osteoporosis Foundation

7. Phosphate balance via diet – Function: with calcium forms hydroxyapatite. Mechanism: adequate, not excessive, intake supports mineralization; avoid very high cola/processed phosphate loads. (General bone nutrition guidance.)

8. Omega-3 fatty acids (food first) – Function: anti-inflammatory support for joints and muscles during rehab. Mechanism: eicosanoid shift may reduce soreness and support activity; not a bone drug. (Adjunct only.)

9. Manganese (trace) – Dose: RDA from diet; avoid excess. Function: enzyme cofactor in bone formation. Mechanism: supports matrix enzymes; deficiency can impair bone in animals. Office of Dietary Supplements

10. Balanced multivitamin/mineral – Function: fills small micronutrient gaps (A, C, Zn, Cu) needed for collagen crosslinking and healing. Mechanism: supports enzymes that build and repair bone matrix. (Adjunct to diet; avoid megadoses.)

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Regenerative / immunity / stem-cell–related therapies

(There are no FDA-approved systemic stem-cell drugs for CDL-BFS or OI. Items below are either biologic devices used locally in surgery or investigational cell therapies. Use only in trials or approved surgical indications.)

1. Romosozumab (Evenity®) – an anabolic antibody that frees Wnt signaling to form new bone. Dose: 210 mg SC monthly (12 months). Function: fast BMD gains in high-risk adults. Mechanism: blocks sclerostin → ↑formation, ↓resorption. (Not for children; CV risk warning.) FDA Access Data

2. Teriparatide (Forteo®) – anabolic systemic builder for selected adults. Dose: 20 mcg SC daily for a limited course. Mechanism: intermittent PTH stimulates osteoblasts to lay new bone. (Not for children.) FDA Access Data

3. Abaloparatide (Tymlos®) – anabolic PTHrP analog. Dose: 80 mcg SC daily (limited duration). Mechanism: osteoblast stimulation. FDA Access Data

4. rhBMP-2 (INFUSE® Bone Graft) – local osteoinductive biologic a surgeon places at the operation site. Function: induces bone formation to aid fusion or fracture repair in approved indications. Mechanism: BMP-2 drives progenitors to become bone-forming cells. FDA Access Data+1

5. Mesenchymal stem cell (MSC) therapy – investigational
   Function: aims to add healthy bone-forming cells and paracrine signals. Mechanism: MSCs may engraft or release factors that support bone formation and reduce fractures. Early human studies and ongoing trials (e.g., BOOSTB4) suggest potential benefits but remain experimental. Dose: protocol-specific in trials. BMJ Open+1

6. Nutritional immune support (vaccination and deficiency correction)
   Function: keep infections low and healing strong. Mechanism: routine vaccines and fixing vitamin D/protein deficits help overall recovery; these are not “immune boosters” but standard health maintenance. (General supportive care.)

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Surgeries

1. Telescopic intramedullary rodding (Fassier–Duval)
   Procedure: surgeons insert growing rods inside long bones to correct bowing and prevent repeat fractures. Why: to straighten bones, allow safer walking, and reduce future breaks as the child grows. Pega Medical+1

2. Osteotomy with internal fixation
   Procedure: controlled bone cuts to realign a deformed limb, then rods/plates hold it straight. Why: align load through the bone to reduce pain and fracture risk and improve gait. ScienceDirect

3. Spinal deformity surgery (select cases)
   Procedure: instrumentation and fusion for severe scoliosis/kyphosis causing pain or breathing issues. Why: protect lung function, posture, and sitting balance in advanced cases. Medscape

4. Management of symptomatic skull lesions
   Procedure: neurosurgical biopsy/decompression only if a calvarial lesion causes pain, pressure, or diagnostic doubt. Why: confirm diagnosis or relieve pressure; many lesions need no surgery. Orpha

5. Fracture fixation and revision of hardware
   Procedure: casting, nails, plates, or revision of migrated telescopic rods. Why: restore alignment, speed healing, and maintain function. MDPI

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Preventions

1. Keep vitamin D and calcium in the healthy range (diet first). Office of Dietary Supplements+1

2. No smoking; limit alcohol to protect bone. Medscape

3. Build leg and core strength with therapist-guided exercises. PMC

4. Make the home fall-safe (lights, rails, no loose rugs). Medscape

5. Use braces or assistive devices when advised. Physiopedia

6. Safe sports: swimming, cycling on a trainer; avoid high-impact/contact. Physiopedia

7. Treat vision problems and review meds that cause dizziness. (General fall prevention.)

8. Dental care before antiresorptives to reduce ONJ risk. (Standard osteoporosis practice.)

9. Vaccinations & infection control to maintain strength for rehab. (General supportive care.)

10. Regular specialist follow-up for dose timing and surgery planning. Dove Medical Press

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When to see a doctor urgently

• New fracture or sudden bone pain after minor movement.

• Headache, scalp tenderness, or neurologic symptoms with skull lesions.

• Back pain with tingling, weakness, or bowel/bladder changes.

• Fever, swelling, or drainage near surgical sites or rods.

• Jaw pain or exposed jawbone after dental work while on antiresorptives.

• Dizziness, fainting, chest pain, or shortness of breath (drug warning symptoms). (General red-flag guidance consistent with osteoporosis drug labels.) FDA Access Data+1

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What to eat and what to avoid

Eat more of:

1. Dairy or fortified alternatives for calcium.

2. Oily fish, eggs, or fortified foods for vitamin D.

3. Leafy greens for vitamin K (check warfarin).

4. Beans, nuts, whole grains for magnesium.

5. Lean proteins (eggs, fish, legumes) for collagen building.

Avoid or limit:

1. Sugary sodas and high-phosphate processed foods that can upset mineral balance.
2. Heavy alcohol (hurts balance and bone cells).
3. Smoking (damages bone and healing).
4. Crash diets (muscle loss → falls).
5. Ultra-high doses of any supplement without labs/doctor guidance. Office of Dietary Supplements+1

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FAQs

1. Is CDL-BFS the same as osteogenesis imperfecta?
   No. They overlap in “brittle bones,” but CDL-BFS is usually caused by SGMS2 variants and has skull “doughnut” lesions; OI is most often due to collagen genes. Treatments often overlap. Frontiers

2. How is it diagnosed?
   By history of easy fractures, low bone density, skull imaging, and genetic testing for SGMS2 (and rarely IFITM5). NCBI+1

3. Will medicines cure it?
   Medicines can strengthen bone and lower fractures but do not change the gene. Long-term follow-up is needed. PubMed

4. Do children and adults get the same drugs?
   No. Several medicines (e.g., teriparatide, romosozumab) are adult-only. Pediatric protocols often use IV bisphosphonates under specialist care. FDA Access Data+1

5. Are bisphosphonates safe?
   They are standard in many brittle-bone disorders. Side effects exist (e.g., hypocalcemia, rare jaw problems). Benefits often outweigh risks when used correctly. FDA Access Data

6. Can denosumab be stopped anytime?
   No. Stopping without follow-on therapy can cause rapid bone loss and fractures. Plan exits carefully with your doctor. FDA Access Data

7. What if I cannot take pills because of my stomach?
   IV options (zoledronic acid, ibandronate, pamidronate) avoid the esophagus and may fit better. FDA Access Data+1

8. Are stem-cell treatments available?
   Only in clinical trials now. Early studies suggest possible benefits, but they are not established routine care. BMJ Open

9. Why are rods used in children?
   Growing rods straighten bowed bones, prevent new fractures, and allow growth—especially in femur and tibia. Pega Medical

10. What is the role of vitamin D and calcium?
    They are the foundation for any bone therapy. Low levels blunt the benefit of other medicines. Office of Dietary Supplements+1

11. Can exercise cause fractures?
    High-impact and contact sports can. Therapist-guided low-impact and water exercises are safe and helpful. PMC

12. Will the skull lesions need surgery?
    Usually not. Surgery is considered only if painful, compressive, or unclear in diagnosis. Orpha

13. Do women need special care after menopause?
    Yes. Bone loss speeds up. Discuss antiresorptives or anabolic therapy if fracture risk is high. FDA Access Data

14. Can diet alone fix bone fragility?
    Diet supports bone but does not replace medical and surgical care in genetic bone disease. Office of Dietary Supplements

15. Who should coordinate care?
    A team: genetics, endocrinology/metabolic bone specialist, orthopedics, PT/OT, dentistry, and primary care. Dove Medical Press

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: November 08, 2025.

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